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.