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
Institute for Medical Research and 1Institute for Medical
Research, Military Medical Academy, Beograd, Yugoslavia
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
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