Decreased interleukin 2 inhibitor in sera of patients with autoimmune disorders

The lymphokine, interleukin 2 (IL-2), is an important modulator of cell-mediated immune (CMI) responses. We report here the detection of an inhibitor of IL-2 in normal sera by measuring the inhibition of thymidine incorporation in IL-2 dependent murine CTLL cells. The inhibitor, partially purified by Sephacryl S-200 gel filtration, eluted with the 60,000-70,000 mol. wt fraction. The factor was destroyed at 56 degrees C for 30 min and did not bind to Protein A Sepharose, suggesting that it is not an immunoglobulin G. Of 26 normal sera tested, 23 had significant levels of the inhibitor. Since connective tissue diseases are often associated with deficient CMI responses, we examined the levels of IL-2 inhibitor in 26 systemic lupus erythematosus (SLE) and 22 rheumatoid arthritis (RA) patients. Only 8 SLE and 12 RA patients had normal levels of the inhibitor. Of the 18 SLE patients with low or undetectable levels, 15 had clinically defined active disease and of the eight with normal levels, three had active disease. The decrease in the IL-2 inhibitor level did not correlate either with steroid or cyclophosphamide treatment or with serum levels of DNA binding and C3. These data suggest that the function of the inhibitor is to control IL-2 activity under normal conditions. Decreased levels of the IL-2 inhibitor in these patients might be explained either as a reduced requirement of this regulatory protein secondary to decreased IL-2 production or a defect of the cells responsible for the production of both IL-2 and its inhibitor.