Effects of treatment with interleukin-1 receptor antagonist on endogenous interleukin-1 levels in normal and irradiated mice

The in vivo effects of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) administration on endogenous IL-1 levels in the circulation and conditioned media (CM) from different immunohematopoietic organ/tissues wer e studied in CBA mice under steady state and postirradiation conditions. In normal mice, constitutive IL-1 levels were demonstrated in the plasma, CM of peritoneal exudate cells and full-thickness skin explants with low or un detectable levels in CM of splenic and bone marrow cell suspensions. In irr adiated mice (2 Gy, X rays) on day 3 post exposure a significant increase o f IL-1 levels was seen in the circulation and CM of peritoneal exudate cell s, with no significantly different levels in postirradiation bone marrow, s pleen and skin. After rhIL-1Ra treatment of the animals (2 x 50 mu g/mouse, i.p.), significantly elevated IL-1 levels were observed in the skin and CM of peritoneal exudate cells in normal mice, whereas slightly increased lev els were detected in CM of splenic cells. The rhIL-1Ra administration in ir radiated mice led to decreased IL-1 concentrations in the circulation, and CM of peritoneal exudate cells and skin. The results pointed out the import ance of IL-1 secretion and receptor expression in the maintenance of homeos tasis in steady state, as well as during recovery after irradiation. Modula tory effects of IL-1Ra on IL-1 production were dependent on basic endogenou s IL-1 concentration.