Interleukin‐1–inhibitory IgG in sera from some patients with rheumatoid arthritis

Abstract

Inhibition of interleukin‐1°aL (IL‐1°aL) activity was detected in 7 of 41 serum samples from patients with rheumatoid arthritis (RA). These 7 sera inhibited not only IL‐1°aL–induced endothelial cell adherence to neutrophils, but also IL‐1°bT–induced endothelial cell adherence, although to a lesser extent. These sera showed no influence on tumor necrosis factor–induced endothelial cell adherence. No inhibitory activity was found in 40 sera from normal control subjects. Studies to further examine these effects included gel filtration analysis of 2 of the RA sera. The inhibitory activity was eluted near Mr 158 kd and above Mr 250 kd. Analysis by protein A affinity chromatography showed that IL‐1–inhibitory activity was present in protein A–binding fractions. Purified IgG (by DE‐52 column chromatography) from RA patients was found to be as potent an inhibitor as the protein A–binding fractions, which suggests that the major inhibitory activity in RA sera is attributable to IgG molecules. These purified IgG molecules also inhibited IL‐1–induced proliferation of mouse thymocytes but did not influence IL‐2–dependent proliferation of the CTLL‐2 murine T cell line. The 7 patients whose sera showed IL‐1–inhibitory activity had mild RA and low titers of rheumatoid factor. The findings, taken together, suggest a possible regulatory role of IL‐1–inhibitory IgG in RA disease activity.

The effect of an interleukin‐1 receptor antagonist protein on type ii collagen–induced arthritis and antigen‐induced arthritis in mice

“…A binding protein specific for IL-1p has been found in RA serum and synovial fluid (37); this may be a soluble form of the type I1 IL-1 receptor identified in Raji B cell supernatants (38). Two other IL-1 inhibitors have been described: endogenously produced anti-IL-1 a antibody (39) and an IL-la-specific binding protein purified from RA synovial fluid (40) which may also be an antibody or antibody fragment. Measurement of these IL-1 antagonists and binding proteins will help determine whether imbalances between IL-1 and its endogenous inhibitors contribute to the pathology of inflammatory diseases such as rheumatoid arthritis.…”

High Levels of Neutralizing Autoantibodies Against IL‐1α are Associated with a Better Prognosis in Chronic Polyarthritis: a Follow‐Up Study

“…Specific regulation of IL-1 involves various natural mechanisms including soluble IL-1 receptors, IL-1 receptor antagonist (IL-1Ra) and anti-IL-1 antibodies [3][4][5]. Such natural autoantibodies to IL-1a were detected in the sera of patients with various autoimmune disorders including RA [6][7][8][9][10][11][12]. More recently, neutralizing anti-IL-1a antibodies were found in a subset of patients characterized by an increased proportion of primary Sjögren's syndrome or self-limited inflammatory arthritis, with limited joint inflammation and destruction [13].…”

Binding of cytokines to pharmaceutically prepared human immunoglobulin.

“…Different assays have been used to measure these antibodies: Western blotting ( 5-10), competition in RIAs and ELISAs (11)(12)(13)(14), binding in direct ELISAs (8-10, 15, 16), binding of radiolabeled cytokines (12)(13)(14)(17)(18)(19)(20)(21)(22)(23), and biological interfer-ence assays (7,8,10,15,17,(24)(25)(26)(27). However, other serum factors than antibodies may compete in RIAs and ELISAs, and inhibition of biological activities may be caused by many factors apart from neutralizing antibodies to cytokines (28)(29)(30)(31).…”