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 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 microg/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.
Bugarski
D
D
Institute for Medical Research, Military Medical Academy, Beograd, Yugoslavia. dianab@imi.bg.ac.yu
Jovcić
G
G
Kataranovski
M
M
Ivanović
Z
Z
Petakov
M
M
Stojanović
N
N
Milenković
P
P
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D006706:Homeostasis / Q000187:drug effects / Q000528:radiation effects; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis / Q000097:blood*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D012795:Sialoglycoproteins / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects
D017077:Culture Media, Conditioned; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins