HIGH-AFFINITY IGG AUTOANTIBODIES TO IL-6 IN SERA OF NORMAL INDIVIDUALS ARE COMPETITIVE INHIBITORS OF IL-6 INVITRO

Nano- to picomolar concentrations of high affinity IgG antibody to interleukin 6 (IL-6ab) were detected in sera of 71 of 467 normal Danish blood donors (15%). IL-6 bound to the Fab fragments of IL-6ab, and the antibody specifically and competitively interfered with enzyme-linked immunosorbent assays for human IL-6. Only IL-6ab-positive sera interfered with these ELISAs. A statistically positive correlation was found between total IL-6 binding and specific IL-6 binding to serum (P < 0.0001), suggesting that IL-6ab dominates as IL-6 binding factors in normal human serum. The IL-6ab also inhibited binding of IL-6 to receptors on the human U-937 macrophage-like cell line, the human U-266 myeloma cell line and the mouse hybridoma cell line B13.29, clone B9 (B9 cells). IL-6-induced proliferation of the B9 cells was competitively inhibited by IL-6ab. We conclude that sera of normal individuals may contain appreciable levels of autoantibodies to IL-6. These IgG autoantibodies may be physiologically and pathophysiologically important because they are potent inhibitors of IL-6 in vitro. © 1993.