Multiple inhibitors of mitogen-induced proliferation of normal lymphocytes in juvenile chronic arthritis sera

We evaluated the effect of 47 serum samples obtained from 34 children with juvenile chronic arthritis (JCA) on mitogen-induced proliferation of normal peripheral blood lymphocytes (nPBL). We found that sera from patients with active disease, and particularly those with the systemic form, inhibited significantly PHA-induced proliferation of nPBL at all the PHA concentrations tested. This inhibitory activity was independent of the treatment and was correlated with the value of the erythrocyte sedimentation rate. Part of the JCA sera inhibitory effect could be reversed by the addition of exogenous interleukin 2 (IL-2), but not of interleukin 1 (IL-1) or interferon-gamma, moreover, JCA sera were able to partially inhibit the IL-2 dependent proliferation of CTLL. When we tested serum fractions obtained by Sephadex G-200 chromatography for their inhibitory activity, we observed that: a) two major peaks of inhibitory activity on PHA-induced proliferation were present: peak 1 with MW less than 600,000 and peak 2 with MW between 70,000 and 35,000; b) the inhibitory activity present in the high MW peak was in part IL-2 related; and c) both peaks contained elevated levels of acute phase proteins (APP) which are known to inhibit mitogen-induced lymphocyte proliferation. We conclude that sera from patients with active systemic JCA contain inhibitory activity on mitogen-induced lymphocyte proliferation. We conclude that sera from patients with active systemic JCA contain inhibitory activity on mitogen-induced lymphocyte proliferation. This activity is due to the presence of multiple inhibitors, one of which appears to be IL-2 related; at least part of the inhibitory activity may be due to elevated serum levels of APP.