The effect of interleukin 1 on IgG synthesis in systemic lupus erythematosus.
The influence of interleukin 1 (IL-1) on IgG synthesis was studied in patients with systemic lupus erythematosus (SLE). Spontaneous IgG synthesis was assessed by culturing peripheral blood mononuclear cells in media for 7 days. The effect of adherent cell supernatants (ACS) on spontaneous IgG synthesis was also assessed, based upon previous studies showing that ACS contributes significantly more to IgG synthesis in SLE than it does in normals. Antiserum against IL-1 reduced spontaneous IgG synthesis by approximately 90% in SLE and normal mononuclear cell cultures. The antiserum caused a parallel reduction in the number of Ig-secreting B cells. Adsorption of SLE ACS with Sepharose-bound antiserum against IL-1 prevented ACS-induced increases in IgG synthesis. Affinity-purified or recombinant IL-1 added to media did not significantly stimulate IgG synthesis. Incubation of ACS with a monoclonal antibody against interferon-gamma had no effect on IgG synthesis, and no detectable interferon activity was found in ACS using a virus inhibition assay. Stimulation of IgG production by autologous mononuclear cell supernatants correlated directly with the presence of clinically active disease, suggesting that these in vitro observations may be important to the disease process. These findings demonstrate that hyperactive B cells from patients with SLE are regulated by factors released by adherent mononuclear cells, probably monocytes. The presence of IL-1 is crucial, but may not be sufficient, for spontaneous and ACS-induced IgG synthesis. Inhibiting or blocking the production of IL-1 may provide a means of reducing abnormal immunoglobulin synthesis in SLE.
D000911:Antibodies, Monoclonal / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007375:Interleukin-1; D007371:Interferon-gamma