Abstract
In 1974, in Nature, one of us has proposed a radically new idea that led to the development of anticytokine therapy which is now used around the world for the treatment of autoimmune diseases. We were the first to use antibodies to IFN-γ and were some of the first to suggest using antagonists of TNF-α in the treatment of autoimmune and inflammatory diseases as well. Our method suppresses one of the main pathogenetic mechanisms of these diseases. Antibodies to IFN-γ and TNF-α exhibit dramatic effects on clinical manifestations of rheumatoid arthritis (RA). However, in our trial ultrasound assessment of the synovial membrane thickness in RA patients showed that only anti-IFN-γ exerted pronounced anti-inflammatory effect. Some patients who underwent treatment with antibodies to TNF-α developed a number of complications. Anticytokine therapy (mono- and poly-) alone or in combination with other drugs can possibly be used not only in the treatment of autoimmune diseases, but also in other pathologies with cytokine synthesis disturbances (a number of neurological, psychiatric, endocrine, and other diseases).
Highlights
In 1974 one of us proposed that a disturbance in IFN synthesis can lead to the development of autoimmune diseases and that antibodies to IFN could be therapeutic [1]
In this report we present results of a larger randomized, double-blind, placebo-controlled trial of anti-IFN-γ and anti-TNF-α therapies administered to separate groups of patients with rheumatoid arthritis (RA)
In previous trials it was established that anti-IFN-γ was a well-tolerated and effective preparation in reducing disease activity in patients with severe RA who failed to respond to any disease-modifying anti-rheumatic drug (DMARD) [3] [4]
Summary
In 1974 one of us proposed that a disturbance in IFN synthesis can lead to the development of autoimmune diseases and that antibodies to IFN could be therapeutic [1] In those times there were only three known types of interferon—alpha, beta, and gamma, which were later classified as cytokines. Cytokines are small molecular weight proteins, glycoproteins and peptides which, among other functions, are involved in cell signaling between immunocompetent cells. In certain cases they serve as anti-inflammatory agents while in others they stimulate inflammation, regulate certain functions of different organs and systems, and cause cell death. Any breakdown of cytokine synthesis leads to a disease state
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