Suppression of IL-2-induced SAA gene expression in mice by the administration of an IL-1 receptor antagonist.
The hepatic acute phase response induced by the administration of interleukin (IL)-2 is most likely mediated by secondary cytokines. In this investigation, we examined the role of endogenous IL-1 in the synthesis of the hepatic acute phase protein serum amyloid A (SAA) during IL-2 treatment. The injection of IL-2 induced SAA gene expression in the liver. The concurrent administration of an IL-1 receptor antagonist (IL-1RA) markedly reduced hepatic SAA mRNA levels and, to a lesser extent, SAA protein levels in the serum. Although IL-1 is an inducer of IL-6 production, the administration of the IL-1RA had no effect on circulating IL-6 levels in IL-2-treated mice. These findings suggest that the production of IL-1 is an important factor in the induction of SAA mRNA in mice undergoing immunotherapy with IL-2.
Numerof
R P
RP
Department of Medicine, New England Medical Center, Boston, MA 02111.
Sipe
J D
JD
Trehu
E G
EG
Dinarello
C A
CA
Mier
J W
JW
D000818:Animals; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D000685:Serum Amyloid A Protein / Q000096:biosynthesis / Q000235:genetics*
D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D000685:Serum Amyloid A Protein