Anti-interleukin-6 antibodies in normal human serum

High-avidity IgG antibodies to the cytokine interleukin-6 (IL-6) were found in sera of apparently healthy adult individuals. These antibodies specifically interfered with an ELISA (enzyme-linked immunosorbent assay) for IL-6 in which specific polyclonal rabbit antibodies to human recombinant IL-6 (rIL-6) were used. Furthermore, using precipitation of 125I-rIL-6 with rabbit antibodies to human immunoglobulins (Ig), the sera of 7 out of 68 Danish blood donors were found to contain specific antibodies in substantial amounts. Judged by ELISA interference, gel filtration of sera incubated with 125I-rIL-6 and second antibody precipitation of 125I-rIL-6, IgG seemed to be the dominant IL-6 binding protein in these normal sera. Using specific antibodies to human Ig light chains, it was found that the anti-IL-6 antibodies were of polyclonal origin. Moreover, there are at least two epitopes on the IL-6 molecule, because more than one IgG bound to some IL-6 molecules at the same time. The anti-IL-6 antibodies did not cross-react with a number of other human recombinant-derived and native cytokines. The antibodies recognized native as well as rIL-6, but preferentially monomeric IL-6.