INCREASED INTERLEUKIN-4 PRODUCTION IN RESPONSE TO MAST-CELL MEDIATORSAND HUMAN TYPE-I COLLAGEN IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Mast cell synovial hyperplasia can occur in patients with rheumatoid a rthritis. Histamine can accelerate synovitis and heparin can inhibit l ymphocyte function. Since interleukin-4 (IL-4) can stimulate murine ma st cell and IgE synthesis, we determined whether mast cell mediators a nd anti-IL-4 might effect lymphocyte proliferation from patients with rheumatoid arthritis. Twenty-four patients with rheumatoid arthritis a nd nine normal controls were evaluated by history, physical examinatio n, physician and patient-assessed joint and allergic symptoms, and dia ry scores. An IL-2-driven-T cell (3H) Tdr proliferation assay with mon oclonal anti-IL-4 and a sensitive Alares were performed with isolated peripheral blood mononuclear cells (PBMC) with 10 mu g/mL of either co ncanavalin A (Con A), type I human collagen, or heparin and 10(-6) M h istamine. Increased lymphocyte proliferation indices with Con A (mean 21.69 +/- 4.9; 6.54 +/- 3.2 normal controls), type I human collagen (m ean 2.17 +/- 0.52, 1.1 +/- .17, normal controls), histamine (mean 1.66 +/- .36; 0.62 +/- 0.08, normal controls), heparin (mean 1.61 +/- .38; 0.69 +/- .11, normal controls) occurred in peripheral blood mononucle ar cells from all patients with rheumatoid arthritis compared with nor mal controls (P<.0236 to .0015) which was inhibited in 32% of peripher al blood mononuclear cells by anti-IL-4. Increased IL-4 ELISA levels i n cultured supernatants were noted with heparin (P<.025) and collagen (P<.05). When peripheral blood mononuclear cells from all patients wit h rheumatoid arthritis were divided into atopic and nonatopic groups, decreased lymphocyte proliferation with histamine (mean 1.06 +/- .20), heparin (mean .96 +/- .19), and collagen (mean 1.5 +/- .20) occurred in 90% of cultures from atopic patients with rheumatoid arthritis with allergic scores (>10) compared with levels in cultures from nonatopic patients with rheumatoid arthritis. Peripheral blood mononuclear cell s from atopic patients with rheumatoid arthritis stimulated with hista mine were significantly more proliferative and inhibited by anti-IL-4 compared with peripheral blood mononuclear cells from normal controls, P <.05. Increased lymphocyte proliferation in all nonatopic patients with rheumatoid arthritis with histamine (mean 1.80 +/- .69), heparin (mean 1.33 +/- .27), and collagen (mean 2.8 +/- 1.0) paralleled decrea sed allergic scores. A possible feedback mechanism in peripheral blood mononuclear cells from atopic patients with rheumatoid arthritis due to IL-4 compared with peripheral blood mononuclear cells from nonatopi c patients might occur with decreased T cell proliferation in the pres ence of mast cell mediators.