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Biomedical subjects

S Skurkovich

Publications and source records attributed to S Skurkovich.

10 recordsLinked to original sources
PubMed2006

Inhibition of IFN-gamma as a method of treatment of various autoimmune diseases, including skin diseases.

We pioneered anticytokine therapy (ACT) for autoimmune diseases (ADs). In 1974, we proposed that hyperproduced interferon (IFN) can bring AD and anti-IFN can be therapeutic. In 1989, we proposed removing tumor necrosis factor (TNF)-alpha together with certain types of IFN to treat various ADs. We found IFN in patients with different ADs and conducted the first clinical trial of ACT in 1975. Anti-IFN-gamma and anti-TNF-alpha work in similar ways, but the latter brings serious complications in some patients. We obtained good, sometimes striking, therapeutic effects treating many different Th-1-mediated ADs with anti-IFN-gamma, including rheumatoid arthritis, multiple sclerosis (MS), corneal transplant rejection, and various autoimmune skin diseases such as psoriasis, alopecia areata, vitiligo, acne vulgaris, and others. Anti-IFN-gamma was in some ways superior to anti-TNF-alpha, which was ineffective in MS. Anti-IFN-gamma therapy holds great promise for treating many Th-1 ADs, especially skin diseases.

Antibodies↗
PubMed2001

Randomized, double-blind trial of anti-interferon-gamma antibodies in rheumatoid arthritis.

INTRODUCTION: An increasing body of evidence indicates that interferon (IFN )-gamma is an immunoregulator and may play a key role in the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). OBJECTIVE: To assess the efficacy and tolerability of anti-IFN-gamma in patients with active RA. METHODS: In a randomized, double-blind trial, 30 patients with active RA were randomly assigned to receive intramuscular injections of anti-IFN-gamma, anti-TNF-alpha, or placebo for 5 consecutive days. RESULTS: Both anti-cytokines were significantly superior to placebo. Patients stopping treatment due to lack of efficacy included I receiving anti-TNF-alpha, 2 receiving anti-IFN-gamma, and 9 receiving placebo. According to the physician's assessment, improvement was achieved by the 7th day in 9 patients receiving anti-TNF-alpha, 7 receiving anti-IFN-gamma, and 2 receiving placebo. By day 28 the corresponding figures were 8, 8, and 0, respectively. CONCLUSION: Antibodies to IFN-gamma could be a promising approach to treating RA, especially its treatment-resistant forms.

Adjuvants, Immunologic↗
PubMed2001

Randomized study of antibodies to IFN-gamma and TNF-alpha in secondary progressive multiple sclerosis.

Studies of cytokines in multiple sclerosis (MS) have shown that immune mechanisms connected with disturbance of the synthesis of cytokines probably play critical roles in the initiation and prolongation of MS. In a double-blind, placebo-controlled trial, 45 patients with active secondary progressive MS were randomized to three groups of 15 patients, each receiving a short course of antibodies to IFN-gamma, to tumor necrosis factor (TNF)-alpha, or a placebo. After 12 months with analysis of disability (Expanded Disability Status Scale scores), accompanied by interval determinations of lymphocyte subpopulations, cytokine production levels, MRI, and evoked potentials, it was found that only patients who received antibodies to IFN-gamma showed statistically significant improvement compared to the placebo group--a significant increase in the number of patients without confirmed disability progression. This was supported by MRI data (a decrease in the number of active lesions) and systemic changes in cytokine status (a decrease in IL-1beta, TNF-alpha, and IFN-gamma concentrations in supernatants of actvated blood cells of these MS patients and an increase in TGF-beta production). Neutralization of IFN-gamma could be a new approach to treating secondary progressive MS. Long-term administration of humanized monoclonal antibodies to IFN-gamma and simultaneous use of antibodies to IFN-gamma together with IFN-beta products are planned.

Animals↗
PubMed1996

Regulation and characterization of the interferon-alpha present in patients with advanced human immunodeficiency virus type 1 disease.

To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.

Acquired Immunodeficiency Syndrome↗
PubMed1994

A disturbance of interferon synthesis with the hyperproduction of unusual kinds of interferon can trigger autoimmune disease and play a pathogenetic role in AIDS: the removal of these interferons can be therapeutic.

Disturbances of interferon synthesis with the hyperproduction of unusual kinds of interferons may be the initial step which triggers autoimmune disease through a chain of pathological reactions including the disturbances of several immunological and cytokine cascades. Prolonged circulation of this interferon may be a predictive marker of an autoimmune condition; the administration of interferons to animals or humans with autoimmune disease or an underlying or latent autoimmune condition can exacerbate or trigger the disease. Healthy people do not have interferon in their blood. This fundamental disturbance of interferon synthesis can result either from a genetic predisposition or from the influence of certain viruses (or viral particles) or both factors together. AIDS has many features similar to autoimmune disease, including the hyperproduction of aberrant interferon, a type with restricted anti-HIV activity, protectively induced by HIV to allow its continued replication and survival. This interferon stimulates the production of certain cytokines and autoantibodies which help unleash the potentially self-destructive powers of the immune system, bringing immunological chaos. In other words, while usual viruses induce normal interferon, which protects the cells against viral infection, HIV induces an abnormal, defective kind of interferon which ensures virus survival. Since there is no known effective method of destroying HIV directly, removing links in this chain of reactions could indirectly destroy HIV and possibly help restore immune functioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1993

A disturbance of interferon synthesis with the hyperproduction of unusual kinds of interferon can trigger autoimmune disease and play a pathogenetic role in AIDS: the removal of these interferons can be therapeutic.

Disturbances of interferon synthesis with the hyperproduction of unusual kinds of interferons may be the initial step which triggers autoimmune disease through a concatenation of pathological reactions including the disturbance of several immunological and interferon cascades. This fundamental disturbance can result either from a genetic predisposition or from the influence of certain viruses (or viral particles) or both factors together. The administration of interferons to individuals with an underlying or latent autoimmune condition can exacerbate or trigger the disease. AIDS has many features similar to autoimmune disease, including the hyperproduction of aberrant interferon, a type with little or no anti-HIV activity, protectively induced by HIV to allow its continued replication and survival. In other words, while most viruses induce normal IFN which protects the cells against viral infection, HIV induces an abnormal, defective kind of IFN which insures viral survival. The neutralization of hyperproduced interferons by polyclonal or monoclonal antibody produced in mouse, or preferably, human hybridoma, removal via extracorporeal means, or the use of antagonists which diminish the production or biological activity of these interferons can be a therapeutic approach to the management of these chronic diseases. In addition, the extracorporeal removal of different kinds of interferons, autoantibodies, autoantigens and other substances from the organism in certain pathological conditions may be an effective and safe method of treatment for autoimmune diseases and AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

A unifying model of the immunoregulatory role of the interferon system: can interferon produce disease in humans?

This hypothesis is a presentation of a unifying model of the interferon (IFN) system as a cascade of sequentially interacting responses of IFNs-alpha, -beta, and -gamma involved in modulation of the immune response. We propose that every antigen is an IFNogen. The first stage(s) of immune responsiveness is associated primarily with the production of the family of IFN-alpha. In certain immunologically mediated diseases, including the autoimmune diseases and AIDS, disturbances in the synthesis of IFN-alpha occur with a switch to the production of predominantly acid-labile types, which have a negative immunoregulatory effect. Moreover, disturbances of IFN synthesis in the embryo or fetus can lead to deformities. Some viruses and other biological and chemical substances manifest a pathological effect by the IFN they induce. This IFN may help sustain the viruses and other substances which induce this IFN. We think it is unsafe to give patients immunoregulators in incomplete form. Thus, there is a potential danger in giving patients recombinant forms of IFNs and interleukin 2 produced in bacteria. In certain immune disorders, we may be able to treat patients by the binding or removal of hyperproduced IFNs from the body. This may lead to the restoration of immunologic balance and clinical improvement.

Antibody Formation↗
PubMed1983

Interferon increases IgE binding to basophils.

One of the pivotal manifestations of immediate type hypersensitivity is mediator release from a variety of mediator cells, e.g., mast cells and basophils. The essential step of this process is the binding of immunoglobulin E (IgE) to the surface of these cells. In the present studies we examined the influence of human interferon (HuIFN) on the binding of IgE to human leukocytes (basophils). The results of these studies indicate that pre-treatment of leukocytes (basophils) with different types of IFN leads to a pronounced increase in binding of IgE to these cells. These data support the hypothesis concerning a pathogenetic role of IFN in the development of allergy of the immediate type hypersensitivity.

Basophils↗