Effects of Treatment with Interleukin-1 Receptor Antagonist on Endogenous Interleukin-1 Levels in Normal and Irradiated Mice

D. Bugarski, G. Jovčić, M. Kataranovski¹, Z. Ivanović, M. Petakov, N. Stojanović, P. Milenković

Received July 29, 1999
Accepted October 26, 1999

Summary
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 were 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 undetectable levels in CM of splenic and bone marrow cell suspensions. In irradiated mice (2 Gy, X rays) on day 3 post exposure a significant increase of IL-1 levels was seen in the circulation and CM of peritoneal exudate cells, with no significantly different levels in postirradiation bone marrow, spleen and skin. After rhIL-1Ra treatment of the animals (2 x 50 mg/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 levels were detected in CM of splenic cells. The rhIL-1Ra administration in irradiated mice led to decreased IL-1 concentrations in the circulation, and CM of peritoneal exudate cells and skin. The results pointed out the importance of IL-1 secretion and receptor expression in the maintenance of homeostasis in steady state, as well as during recovery after irradiation. Modulatory effects of IL-1Ra on IL-1 production were dependent on basic endogenous IL-1 concentration.

Key words
rhIL-1Ra · IL-1 · In vivo · Steady-state · Irradiation

Reprint requests
Dr Diana Bugarski, Institute for Medical Research, Dr Subotića 4, P.O.Box 102, 11129 Beograd, Yugoslavia, e-mail: dianab@imi.bg.ac.yu