Immunotherapy & Autoimmune faq's


Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Studies in humans and experimental animal models are revealing the genetic and environmental factors that contribute to autoimmunity. A major goal of research in this area is to exploit this knowledge to better understand the pathogenesis of autoimmune diseases and to develop strategies for reestablishing the normal balance between effector and regulatory immune responses.

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Autoimmune diseases are a significant clinical problem because of their chronic nature, the associated healthcare cost, and their prevalence in young populations during the prime of their working and peak reproductive years. Current therapies, such as cytokine antagonists, have shown great promise in treating many of these diseases. TNF-α antagonists have changed the course of rheumatoid arthritis, and other cytokine antagonists are showing impressive efficacy in various other diseases (1, 2). However, most of the current therapeutic agents target the terminal phase of inflammation and do not address the fundamental problems that are responsible for the initiation and progression of the autoimmune process. In most cases, this necessitates continued and sometimes life-long therapy, resulting in an increased risk of malignant and infectious complications. Tackling these diseases at their source will require an understanding of how the abnormal immune reactions arise, how they are sustained, and the intrinsic mechanisms used to suppress these responses in healthy individuals.

Autoimmune diseases vary greatly in the organs they affect and in their clinical manifestations, with some being limited to particular tissues and others being systemic or disseminated. Despite these variations, all autoimmune diseases are believed to go through sequential phases of initiation, propagation, and resolution (Figure 1). All stages of autoimmune disease are thought to be associated with a failure of regulatory mechanisms, with the resolution phase defined by a partial, and in most cases, short-term ability to restore the balance of effector and regulatory responses. Augmenting regulatory mechanisms and establishing robust and long-lived disease resolution is a goal of new therapeutic strategies.


Amino acid in Human Autoimmune immunotherapy

ImmunoTherapy is the Best protocol for Autoimmune Disease

 The type I interferon system plays a critical role in host defense in health, and a growing body of literature suggests that type I interferon is a critical mediator of human autoimmune disease (1). Type I interferons function as a bridge between the innate and adaptive immune systems, and as such play an important role in setting thresholds for response against self antigens. Many investigators have focused on the role type I interferons play in autoimmune disease. This fascinating and rapidly growing body of literature encompasses many different autoimmune diseases, including systemic lupus erythematosus, type I diabetes, multiple sclerosis, and others. Type I interferons play differing roles in human autoimmune conditions. 

For example, in the autoimmune diseases, systemic lupus erythematosus and Sjogren’s syndrome, increased interferon alpha signaling plays a pathogenic role (2, 3). Interestingly, interferon beta is used as a therapeutic in multiple sclerosis, an autoimmune disease of the central nervous system (4). Both interferon alpha and beta signal through the same type I interferon receptor and share many similarities in downstream signaling, suggesting that the disparate activities of type I interferons in lupus and multiple sclerosis relate to differences in the underlying disease processes and immunoregulation in these two diseases. In this Research Topic, a series of articles provides a comprehensive overview of the various roles type I interferons play in autoimmune diseases, with a focus on human immunology.

This Research Topic features a number of Original Research Articles, including a study by Mavragani et al. examining type I interferon levels in the organ-specific autoimmune disorders type I diabetes and autoimmune thyroid disease (5). They demonstrate high type I interferon levels in both of these autoimmune conditions, supporting the idea that high levels of type I interferon are detectable in organ-specific autoimmune conditions in addition to systemic autoimmune disorders. Clark et al. investigate genetic polymorphisms in the interferon regulatory factor 5 (IRF5) gene (6). 

This gene has been associated with susceptibility to systemic lupus erythematosus (7), and they demonstrate four distinct promoter regions have differential activity. Ko et al. study type I interferon-induced gene expression in patients with systemic lupus erythematosus (8). They demonstrate that the expression of type I interferon-induced genes in lupus immune cells differs significantly between ancestral backgrounds, which corresponds to clinical differences in the disease between ancestral backgrounds. A Methods article by Feng et al. examines public domain gene expression data to document patterns of type I interferon-induced gene expression and infer both positive and negative regulation by transcription factors 

 The Research Topic also features a number of Review Articles focusing on various disease states. Liu et al. review murine models of systemic lupus erythematosus that are interferon-inducible, providing model systems of autoimmunity related to type I interferon (10). Wu et al. review the role of type I interferon in systemic sclerosis, a distinct autoimmune disease characterized by thickening and fibrosis of the skin, which shares a type I interferon signature with other autoimmune conditions (11). Li et al. review the evidence supporting a role for type I interferon in the pathogenesis of Sjogren’s syndrome, spanning genetic associations, gene expression studies, and clinical features of the disease (12). Reder et al. review the contrasting role of type I interferon in multiple sclerosis and systemic lupus erythematosus and other autoimmune conditions (13).

 In multiple sclerosis, type I interferon levels are low (14), and administration of recombinant type I interferon is an effective treatment. They review the evidence supporting multiple sclerosis as a low interferon autoimmune disease, and speculate on immunological features that might underlie this striking difference. Shrivastav et al. review the role of nucleic acid receptors in type I interferon generation in systemic lupus erythematosus (15), a disease characterized by pathological activation of the type I interferon pathway. These articles taken together provide an overview of many of the ways type I interferons have been implicated in human autoimmune disease, providing a fascinating window into the biology of the human immune system gone wrong. 

autoimmune immunotherapy successes

Type 1 Diabetes

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by the selective destruction of pancreatic β-cells. The histopathology of T1D is defined by a decreased β-cell mass with infiltration of mononuclear cells into the islets of Langerhans, which was described in 1901 by Opie (1). 

    This lesion was later called ‘insulitis’, and it is the hallmark of T1D. In 1965, Gepts reported that insulitis was observed in 70% of patients with acute-onset T1D and concluded that this disease was caused by a β-cell-specific autoimmune process (2). 

Furthermore, in the 1970s, Nerup demonstrated cellular autoimmunity in patients with T1D using the leukocyte migration test and speculated that cellular hypersensitivity was the counterpart of lymphocytic infiltration in islets (3). 

Therefore, he speculated that cell-mediated immunity could play an important part in the pathogenesis of T1D. As a view suggesting that T1D is an autoimmune disease, there is some evidence that T1D is often complicated with other autoimmune diseases or that anti-islet autoantibodies precede the clinical onset of the disease. In this article, I focus on these two points and review the recent knowledge.

Myasthenia Gravis

 Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body.

The thymus may give incorrect instructions to developing immune cells, ultimately resulting in autoimmunity and the production of the acetylcholine receptor antibodies.


 Autoimmune disease of the inner ear is part of the large group of neurosensory hearing losses, of which it represents less than 1%. 

The disease is defined as a rapidly progressive, often fluctuating bilateral sensorineural hearing loss, which evolves over a period of weeks or months and which initially responds to immunosuppressive therapy 


 Lupus (systemic lupus erythematosus) is a serious and potentially fatal disease that mainly affects young women. The cause of the disease is not known, but it is believed to be an autoimmune disease (an illness that occurs when the body mistakenly detects its own tissue as foreign and attacks itself).The disease often starts between the ages of 15 and 44. The manifestations of lupus are diverse: it can affect many parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels, and brain.

An estimated 240,000 Americans are diagnosed with lupus. People of all races can have the disease; however, African American women have a three-times higher incidence (number of new cases) than Caucasian women. They tend to develop the disease at a younger age than Caucasian women and to develop more serious complications. Nine times more women than men have lupus, and it is also more common in women of Hispanic, Asian, and Native American descent. Lupus occurs when your immune system attacks healthy tissue in your body (autoimmune disease). ... The cause of lupus in most cases, however, is unknown 

Graves Disease

 Graves' disease is a type of autoimmune problem that causes the thyroid gland to produce too much thyroid hormone, which is called hyperthyroidism.Graves' disease is often the underlying cause of hyperthyroidism. ... These antibodies are called thyroid-stimulating immunoglobulins 


 Fibromyalgia (FM) is a disorder characterised by soft tissue pain, disturbance of function an often prolonged course and variable fatigue and debility. A clearly defined aetiology has not been described. 

This paper proposes that immunological aberration is likely and this may prove to be associated with an expanding group of novel vasoactive neuropeptides. Vasoactive neuropeptides act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to small peptide fragments. 

They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault and the maintenance of homeostasis. 

Failure of these substances has adverse consequences for homeostasis. This paper describes a biologically plausible mechanism for the development of FM based on loss of immunological tolerance to the vasoactive neuropeptides. The proposed mechanism of action is that inflammatory cytokines are provoked by tissue injury from unaccustomed exercise or physical injury. This may trigger a response by certain vasoactive neuropeptides which then undergo autoimmune dysfunction as well as affecting their receptor binding sites.  

autoimmune immunotherapy successes

Atopic Eczema

 Clinical chemistry data remained unchanged. Immunological studies performed in parallel showed a decrease in total serum IgE of 50% in child 1, a decrease in spontaneous in vitro IgE production, an increase in in vitro production of interleukin-6, and a normalization of previously decreased in vitro lymphocyte responses to several mitogens. 

While marked immunological changes were noted during IFN-gamma treatment, clinical benefits were not encouraging. Diminished IFN-gamma production has been claimed to be a major pathogenic factor in atopic eczema. Our results indicate that the pathogenesis is more complex. Clinically, we were unable to confirm previous observations in adults. Further studies are needed before IFN-gamma can be recommended for therapy of pediatric atopic eczema. 

Sports Muscle and Joint Injuries and improved Recovery with Immunotherapy.

 Muscle injuries are a common problem in sports medicine. Skeletal muscle can regenerate itself, but the process is both slow and incomplete. Previously we and others have used growth factors to improve the regeneration of muscle, but the muscle healing was impeded by scar tissue formation. However, when we blocked the fibrosis process with decorin, an antifibrosis agent, we improved the muscle healing. 

Here we show that gamma interferon (gammaINF)--a cytokine that inhibits the signaling of transforming growth factor beta1 (TGFbeta1), a fibrotic stimulator--reduces fibrosis formation and improves the healing of lacerated skeletal muscle. With gammaINF treatment, the growth rate of muscle-derived fibroblasts was reduced and the level of fibrotic protein expression induced by TGFbeta1 (including TGFbeta1, vimentin, and alpha-smooth muscle actin) was down-regulated in vitro. In a mouse laceration model, the area of fibrosis decreased when gammaINF was injected at either 1 or 2 weeks after injury. 

More importantly, the injection of gammaINF at either 1 or 2 weeks post-injury was found to improve muscle function in terms of both fast-twitch and tetanic strength. This study demonstrates that gammaINF is a potent antifibrosis agent that can improve muscle healing after laceration injury 

Multiple Sclerosis

Type I interferons (IFNs) are important innate and adaptive immunity. They are used to treat virus infections, cancer, and multiple sclerosis (MS). There are 5 type I IFN families in humans—IFN-α with 13 subtypes, plus IFN-β, ɛ, κ, and ω. Because their receptor binding affinities vary, these IFNs have different gene induction profiles and quite variable therapeutic effects. IFN-α subtypes may each be specific for certain viruses, but can be neurotoxic. IFN-β induces IFN-α, plus has additional direct effects on target cells. IFN-β was the first therapy approved that could change the course of MS. It has cognition in MS, and may be neuroprotective and can potentially enhanbroader specificity than IFN-α, enhances ce fertility in women. Priming the IFN signaling system with an injection of IFN-β can enhance subnormal type I IFN signals in MS. Many other commonly used drugs and vitamins may potentiate clinical benefits of IFN-β.

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Type I Interferons and Multiple Sclerosis

Type i interferons (IFNs; IFN-α, β, ɛ, κ, and ω in humans, plus IFN-tau [IFN-τ] in ungulates) are produced by many cells. Typically, fibroblasts produce IFN-β; plasmacytoid dendritic cells (DC) produce IFN-α. Type I IFNs have tissue-specific and gene-specific roles that are dependent on a balance of the different IFN subtypes, the timing of exposure, and interactions with drugs and environmental factors. The ∼1,000 genes that are controlled by these IFNs are critical for antiviral immunity and also impact cell proliferation, immune regulation, cytoprotection, and possibly fertility.

In multiple sclerosis (MS), cells from the innate and adaptive arms of the immune system cause central nervous system (CNS) inflammation. Adaptive immunity is prominent in the earlier, relapsing/remitting phase of MS (RRMS). Innate immune responses appear to underlie the later secondary progressive (SPMS) phase but are likely to contribute to brain damage at all times. IFN-β therapy for MS prevents and shortens relapses and also reduces new magnetic resonance imaging (MRI) brain lesions, MRI T1 black hole formation, progression, and cognitive loss (Lacy and others 2013). 

Long-term therapy induces neuroprotectant proteins such as BDNF, NGF, Nrf2, and NCOA7-AS (Croze and others 2013). Five years of IFN-β-1b therapy, begun 8 years after the first symptoms, reduces the death rate by 47% (Goodin and others 2012). The survival benefit is based on less all-cause mortality, but is predominantly from less MS-related death. Its method of action is complex, with dose-dependent changes in different cells and tissues, and variation at different phases of MS.

Immunotherapy & Alzheimer’s Disease

 The aging immune system responds less vigorously to some unfamiliar new provocations. This is thought to underlie, for example, the smaller production of new antibodies seen in older adults who are vaccinated. It may also help to explain the confusing but common clinical situation that occurs when an older adult with a potentially serious infection presents clinicians with a deceptively small fever or increase in disease-fighting white blood cells.

In some ways, though, the aging immune system also becomes more rather than less active. Our brains, which have a special immune system that is mostly separate from that of the rest of the body, are protected by specialized immune cells called microglia that attack various kinds of diseases with toxic substances including inflammatory cytokines. These substances can produce collateral damage, killing brain cells, and some researchers think the brain’s powerful immune response to amyloid plaques (one of the hallmarks of AD) explains the destructive effects of this brain disease. 


Alzheimer's disease (AD), the most common progressive neurodegenerative disorder in the elderly, is clinically characterized by progressive impairment of cognitive functions, including reduced critical capacity, weakness of decision-making and problem orientation, while in the more advanced stages it is accompanied by behavioral disorders and impaired verbal ability. Neuropathological characteristics of the disease are the neurofibrillary tangles (NFT), the neuritic plaques (NP), the prominent synaptic loss and eventually the neuronal loss. The presence of inflammatory process seems to be playing important role in the progression of the disease. 

This process is directed by the activated glial cells and it leads to the overproduction of acute phase proteins, complement factors activation and induction of inflammatory enzyme systems. These inflammatory factors can contribute to neuronal dysfunction and cell death. Cytokines belong to the acute phase proteins, which are secreted from glial cells. They can either strengthen the inflammatory reaction or suppress it, adjusting the intensity and duration of the immune response. In the category of cytokines belong several interleukins (ILs) and various factors (TNF-α, TGF-β). 

Interleukins are involved in complex intercellular interactions among neurons, microglia and astrocytes, as well as intracellular signal transduction events, which are necessary to promote the inflammatory cascade characteristic of AD neuropathology. It has been observed that increased levels of pro- inflammatory cytokines, including tumor necrosis factor (TNF), interleukin 1β (IL-1β), interleukin 6 (IL-6) and interferon γ (IFN-γ), may suspend phagocytosis of amyloid Aβ in brains of patients with AD. Thus, it may interfere with the effective removal of plaque from microglia, promote astrogliosis and neural death. 

Normally, during immune surveillance, a balance is maintained between pro- and antiinflammatory influences. Yet, during AD, the abnormal accumulation of soluble amyloid oligomers triggers excessive release of pro inflammatory factors, such as cytokines and other acute-phase reactants, out of proportion to the regulatory components, such as IL-4, IL-10, receptor antagonists, interleukin inhibitors and others, ultimately leading to neuronal and synaptic injury and loss and cognitive decline. These changes in the brain parenchyma are often accompanied by changes in levels of these inflammatory proteins in peripheral blood. Even though literature is presenting conflicting studies, efforts are being made for the detection of cytokines in peripheral blood and association of their levels with the progression of AD. 

Inflammatory pathways, involving the signaling of cytokines, could be potential targets for the prevention of AD and the development of new therapies. The aim of the present work is to review studies indicating a correlation between these inflammatory agents and AD pathogenesi

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Immunotherapy and Alzheimer’s Disease: Helping the Body to Help Itself

Alzheimer’s disease (AD) continues to affect the lives of millions of Americans. As our elderly population increases, our need to help patients and caregivers cope with this illness will continue to escalate.  Treatment of AD has already improved vastly as a result of deeper appreciation of patients’ and caregivers’ needs, our growing evidence base for the importance of lifestyle choices, and the availability of medications specifically indicated for the treatment of this brain disease.  

The medications currently approved by the FDA, unfortunately, have modest benefits and do not modify AD’s fundamental disease process. Researchers continue to search for better medications that will supplement other treatment approaches.  In the search for disease-modifying medications, intense interest has focused on how the immune system can be recruited into the fight against AD.

The Function of the Immune System

Our immune systems act constantly to protect our bodies from invasion by infectious agents. In addition, immune system components monitor changes in our bodies’ own cells, for example by eliminating or limiting some cancers.  The cells of the immune system include producers of antibodies and also cells that attack, poison, and scavenge invading organisms or our own damaged cells.  As we age, the immune system becomes both less and more active.

Aging Immune Systems

The aging immune system responds less vigorously to some unfamiliar new provocations. This is thought to underlie, for example, the smaller production of new antibodies seen in older adults who are vaccinated. It may also help to explain the confusing but common clinical situation that occurs when an older adult with a potentially serious infection presents clinicians with a deceptively small fever or increase in disease-fighting white blood cells.

In some ways, though, the aging immune system also becomes more rather than less active. Our brains, which have a special immune system that is mostly separate from that of the rest of the body, are protected by specialized immune cells called microglia that attack various kinds of diseases with toxic substances including inflammatory cytokines. These substances can produce collateral damage, killing brain cells, and some researchers think the brain’s powerful immune response to amyloid plaques 

(one of the hallmarks of AD) explains the destructive effects of this brain disease.

Recruiting the Immune System to Fight Alzheimer’s

Since the 1990s, researchers have been exploring ways in which the immune system’s effects could be recruited into the fight against AD. Early experiments showed that rodents with AD-like plaques induced by genetic manipulation could be immunized against toxic amyloid beta, the protein that aggregates into AD’s characteristic plaques. Remarkably, these experimental immunizations were shown to decrease the amount of brain amyloid (“amyloid load”) in these rodents while also improving their cognitive functioning.

Two Approaches

Immunotherapy, which is the use of immunity-enhancing techniques as a medical treatment, has taken two basic forms in the fight against AD. In active immunization, a fragment of amyloid beta or a related antigen is administered in order to stimulate a response of both antibody-based and cellular immunity. Passive immunization, by contrast, relies upon the intravenous injection of pre-formed antibodies into an animal for the purpose of boosting resistance to the aggregation of amyloid beta or helping the immune system remove amyloid beta already aggregated into plaques.  Although only a small fraction of intravenously administered antibodies pass the blood-brain barrier and enter the brain, their significant effects indicate the potential value of this treatment approach.

Active immunization seemed initially to be the most promising method, because vaccination might induce long-term protection after a small number of relatively inexpensive treatments. Evaluation of the first widely tested human anti-amyloid beta vaccine, however, was stopped in 2002 because its effects included an unacceptably high rate (6%) of meningoencephalitis, a type of central nervous system inflammation that can be fatal.  The hope for an AD vaccine has not been fully abandoned, however, and several new vaccines believed less likely to cause meningoencephalitis are currently in testing.

Passive immunization has appeared a safer treatment approach to many investigators, though it requires repeated infusions and accrues greater expense. Infusion of pooled IGG (gamma globulin) has not proved as effective as originally hoped, but many investigators regard the use of “monoclonal” antibody infusions as promising. Monoclonal antibodies are all of an identical structure and they are designed to attack and help eliminate beta amyloid in various forms. 

 Bapineuzumab, an early member of this class of medications, was pushed to the sideline because of associated adverse effects: brain swelling (vasogenic edema) and focal bleeding (micro-hemorrhages, later termed amyloid-related imaging abnormalities or ARIA). Testing of solanezumab as a treatment for mild dementia, a monoclonal antibody that targeted smaller amyloid beta molecules circulating in the blood, was halted in 2016 when the medication failed to demonstrate efficacy in clinical trials. Other monoclonal antibodies, including aducanamab, are also being tested.  Use of the newer agents is less frequently associated with brain swelling and focal bleeding.

Hope for Early Intervention

The proof of immunotherapy, ultimately, will be its ability to modify the course of AD. It would be fair to say at this point that both active and passive immunization against amyloid beta have been shown to reduce the brain’s amyloid load but not to produce significant cognitive benefit in patients with advanced AD. There is much greater hope, however, for beneficial effects of early intervention. 

Findings suggest that passive immunotherapy at a very early stage may have significant clinical effects, and several large scale trials are now underway to test the effects of passive immunotherapy in prodromal or early Alzheimer's disease in early stage human subjects whose diagnosis has been verified using PET amyloid canning or cerebrospinal fluid analysis. Needless to say, the results of these trials are eagerly awaited by researchers, patients, and caregivers!


Immunotherapy is a powerful treatment approach that holds considerable promise for the future. Already it has improved the management of some serious cancers, and it may similarly improve our care of AD patients.  Among the improvements of immunotherapy already being tested are the targeting of molecules other than amyloid beta, including disordered tau protein, and the development of safer and more effective antibodies. As the future unfolds, immunotherapy may be the first truly disease-modifying weapon in our efforts to reduce the devastating effects of AD.

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Hypereosinophilic syndromes (HES)

 Hypereosinophilic syndromes (HES) and systemic mastocytosis (SMCD) are heterogeneous disorders with clinical symptoms from local and remote effects of excessive proliferation of eosinophils and mast cells, respectively. Interferon alpha (IFN-alpha), alone or in combination with other medications, can be a useful, and at times life-saving, treatment for patients with HES. Receptors for IFN-alpha are present on eosinophils, and clinical benefits are due to its effect on eosinophil proliferation, migration, activation, and survival. 

These effects are likely mediated through multiple pathways including, but not limited to, inhibition of eosinophil colony-forming cells, upregulation of IFN-gamma synthesis, and inhibition of production of eosinophil-active cytokines by T cells, mast cells, and mononuclear cells. IFN-alpha has been life-saving for patients with intractable HES that were resistant to prednisone, hydroxyurea, and other agents. Resistance to the eosinopenic effect of IFN-alpha does not develop and the dose of IFN-alpha necessary to maintain control of eosinophilia often decreases with time. 

The combination of IFN-alpha and hydroxyurea is very useful and allows dosage reduction of IFN-alpha and better control of hypereosinophilia than with either agent alone. The efficacy of IFN-alpha for treatment of SMCD has been more difficult to establish, with both favorable and unfavorable results reported. The disparate results may have resulted from the small number of patients with SMCD treated with IFN-alpha, the use of various criteria for a "successful" treatment outcome, short duration of treatment and follow-up, and the use of modest dosages. 

In reported series, side effects from IFN-alpha have frequently been dose-limiting. IFN-alpha improves many of the clinical symptoms of SMCD including dermatological, hematological, gastrointestinal, and systemic symptoms associated with histamine release. IFN-alpha has a beneficial effect on skeletal symptoms because of its ability to increase bone density and reduce painful episodes from vertebral fractures. No consistent improvement in bone marrow infiltration by mast cells has been demonstrated except in a recent study employing high dosages of IFN-alpha. A beneficial effect from the combination of IFN-alpha and prednisone has been reported for several patients, suggesting that combined use of these two medications may provide synergism in treatment outcomes. 

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 Interferon-alpha (IFN-alpha) is a pleiotropic cytokine belonging to type I IFN, currently used in cancer patients. Early studies in mouse tumor models have shown the importance of host immune mechanisms in the generation of a long-lasting antitumor response to type I IFN. Recent studies have underscored new immunomodulatory effects of IFN-alpha, including activities on T and dendritic cells, which may explain IFN-induced tumor immunity. Reports on new immune correlates in cancer patients responding to IFN-alpha represent additional evidence on the importance of the interactions of IFN-alpha with the immune system for the generation of durable antitumor response. This knowledge, together with results from studies on genetically modified tumor cells expressing IFN-alpha, suggest novel strategies for using these cytokines in cancer immunotherapy and in particular the use of IFN-alpha as an immune adjuvant for the development of cancer vaccines 

Breast Tumor/Cancer

  Although it was initially thought that type I IFNs exert direct anticancer effects by activating IFNAR signalling in malignant cells — hence inhibiting cell cycle progression95, promoting terminal differentiation67 , inducing apoptosis50 or mobilizing stem cells60,96 — it is becoming increasingly clear that type I IFNs mainly function (but perhaps not only) by stimulating anticancer immune responses. Such an immunostimulatory effect can originate from type I IFNs secreted by malignant cells or by intratumoural DCs. Moreover, it can involve autocrine or paracrine signalling circuits induced by stimulation of IFNARs expressed by malignant, vascular and/or immune cell compartments of the tumour mass. Depending on the experimental model, the antineoplastic activity of exogenously administered type I IFNs has indeed been attributed to IFNAR signalling in immune cells35,97,98, endothelial cells99 or malignant cells36. Taken together, these findings suggest that targeting type I IFNs to a specific cellular compartment of the tumour mass may mediate optimal therapeutic effects in some, but not in all, cancers. Irrespective of this unanswered question, type I IFN signalling within neoplastic lesions seems to be essential for both natural and therapy-induced immunosurveillance, which indicates that the expression levels of these cytokines, as well as of their downstream effectors (for example, ISGs), should be further investigated as prognostic and predictive biomarkers. Therapies designed to increase the intratumoural concentration of type I IFNs can have antineoplastic effects following the induction of anticancer immune responses. Thus, it will also be important to optimize the methods to selectively deliver type I IFNs to the tumour bed in a way that results in superior immunostimulatory effects but that avoids possibly detrimental outcomes, such as inducing the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1)100. Moreover, it will be essential to advantageously combine type I IFN (or agents eliciting its production) with other immunostimulatory agents, such as checkpoint blockers28,89,101, granulocyte–macrophage colonystimulating factor (GM­CSF) or other cytokines55,70, and inhibitors of the transcription factor STAT3, which is involved in multiple immunosuppressive circuits102. It can be anticipated that strategies for the appropriate stimulation of type I IFN signalling will lead the way to the development of ever-more effective anticancer therapies. By taking advantage of a sophisticated defence system that originally evolved to clear virus-infected cells, tumour immunologists should dedicate substantial efforts to inducing a state that mimics viral infection,

Chemotherapy/Radiation recovery

Multiple Myeloma

 IFN has been studied in the maintenance setting following induction chemotherapy in patients with multiple myeloma. An early trial from the Italian Myeloma Study Group initially suggested improved survival with IFN maintenance; however, longer follow-up only demonstrated an improved response duration for patients receiving IFN, with no overall survival benefit [110]. Three other trials have demonstrated improved response durations for patients receiving IFN maintenance therapy [111113], with one suggesting a survival benefit. In a randomized trial of IFN maintenance following high-dose melphalan/prednisone followed by autologous bone marrow transplantation, selected patients, those achieving a complete response, survived longer with IFN treatment [114]. Thus, there appears to be an advantage to maintenance therapy with IFN in some patients following induction therapy for multiple myeloma. 

Breast Cancer

 IFN Activity at the Cellular Level: Clinical Implications

The IFNs have been found to produce a large array of molecular and cellular actions of potential relevance to their use in cancer. These include direct growth inhibition of tumor cells, with IFN-β exhibiting greater activity than IFN-α [2829]. The IFNs have well-described actions to induce or inhibit the expression of specific genes [1, 3]. Two IFN-inducible genes that have been best characterized are the 2′-5′ oligoadenylate synthetase and a double-stranded RNA-dependent protein kinase. The activation of these genes leads to increased RNA degradation and inhibition of protein synthesis, respectively. Although the potential role of these genes in the antiviral effects of the IFNs is more clearly defined than in their antitumor actions, expression of a functional defective mutant of human double-stranded RNA-dependent protein kinase in NIH 3T3 cells resulted in malignant transformation [30]. Potentially of greater relevance to the use of IFN in cancer are its modulatory effects on the expression of oncogenes and tumor suppressor genes. Both IFN-α and IFN-γ reduced the expression of the Her-2 proto-oncogene in human breast and ovarian carcinoma cells [31], suppressed the phosphorylation of the retinoblastoma protein [32], reduced expression of the c-mycgene [3335] and reduced the overexpression of the p53 gene [36]. IFN has been shown to antagonize the growth stimulatory effects of serum, epidermal growth factor, and platelet-derived growth factor, in part because of the downregulation of cell surface receptors for the growth factors and the inhibition of other early growth factor-mediated events [3740]. These and related mechanisms may be particularly relevant in the actions of IFN-α in hairy cell leukemia, a rare malignancy that is particularly responsive to IFN therapy. Studies suggest that IFN induces the differentiation of the leukemic cells toward a stage less responsive to growth factor stimulation [41]


 Cytokines. Your body produces proteins called cytokines. They naturally boost your immune system. Doctors sometimes prescribe artificial cytokines for people with melanoma. Research shows the drugs make it harder for cancer cells to divide, and help your body’s immune system respond to the cancerous cells. 

Autoimmune arthritis

Autoimmune Diseases


 The normal human immune system protects us from infection; when its regulation is impaired, it gives rise to these diseases in which normal tissues are attacked and damaged. Attacking self-tissues, beginning in the joints, is the definition of autoimmune arthritis.

The most prevalent forms of autoimmune arthritis are rheumatoid arthritis, juvenile forms of arthritis and lupus. However, there are many other autoimmune forms of arthritis that can be just as debilitating and dangerous.

Arthritis And Aging


 OA is the degradation of joint tissues from the effects of “wear and tear”, injury or repetitive use causing pain, a grinding sensation and inflammation. The breakdown of joint tissues can cause the grinding of bone-on-bone, pain, bone damage, limited joint movement and deformities. However, this form of arthritis does not involve immune system. 

 Osteoarthritis is the degeneration of joint tissues caused by injury, repetitive use or the aging process. When we reach 50, our immune system no longer function at its optimum (typically 20-50 years of age). This may lead to various autoimmune disorders, including autoimmune forms of arthritis such as rheumatoid arthritis and lupus  

Rheumatoid Arthritis


 Rheumatoid arthritis (RA) is a complex disease in which the patient’s immune system attacks its own tissue causing swelling and inflammation in the joints and damage of tissues and other organs. Much of the rheumatoid arthritis research being conducted focuses on immune mechanisms involved. Many of these mechanisms are shared with other autoimmune diseases that attack different organs, such as lupus (kidneys), multiple sclerosis (brain) and Type I diabetes (pancreas). The causes of rheumatoid arthritis are still unknown, but we do know that autoimmune diseases have a start and halt progression, with periods of active disease followed by periods of remission. 



 Systemic Lupus Erythematosus (SLE or Lupus) is a systemic autoimmune disease that affects many joints and organs in the body. In lupus, like rheumatoid arthritis (RA), the patient’s immune system attacks their own healthy tissues. Lupus research funded by LSOW is focused on understanding systemic lupus so we can find new treatments and a cure.

Initially, in Systemic Lupus Erythematosus, the tissues being attacked are different from RA; however, in later stages, the diseases become very similar. 

LSOW funding research on the pathology and causes of lupus is revealing new approaches towards developing therapies and a treatments  Lupus is known as an autoimmune disorder because the body begins to wage battle with itself by destroying healthy tissue. There are four different forms of Lupus that show significantly different symptoms. Because it is an autoimmune disorder much like most forms of arthritis, the Arthritis National Research Foundation (ANRF) provides grants to researchers who are specifically seeking cures and remedy for Lupus 



 Psoriatic Arthritis (PsA) is an autoimmune form of arthritis; an estimated 30% of all psoriasis patients develop psoriatic arthritis. The symptoms of psoriatic arthritis are similar to those of three other types of arthritis: rheumatoid arthritis, gout and reactive arthritis  Psoriatic arthritis is a form of arthritis that affects some people who have psoriasis — a condition that features red patches of skin topped with silvery scales. Most people develop psoriasis first and are later diagnosed with psoriatic arthritis, but the joint problems can sometimes begin before skin lesions appear 



 Gout, a complex and painful form of arthritis, is characterized by sudden, severe attacks of pain, redness and tenderness in joints, often the joint at the base of the big toe. Men are more likely to get gout, but women become increasingly susceptible to gout after menopause. People with kidney disease are also more susceptible. Over 8 million Americans have gout.

Gout occurs when urate crystals accumulate in your joint, causing the inflammation, swelling and intense pain. Urate crystals can form when you have high levels of uric acid in your body, including in the bloodstream (called “hyperuricemia”). Over time, increased uric acid levels in the blood may lead to deposits of urate crystals in and around the joints. These crystals can attract and activate white blood cells, leading to severe, painful gout attacks and chronic arthritis. Uric acid also can deposit in the urinary tract, causing kidney stones..


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