Interleukin 1 receptor antagonist gene expression in rat pituitary in the systemic inflammatory response syndrome: pathophysiological implications.
The systemic inflammatory response syndrome (SIRS) is characterized by endothelial cell activation causing a generalized inflammatory response and cytokine-mediated pathophysiological alterations. The pathophysiology of SIRS involves changes in the functioning of several endocrine glands, including the pituitary. SIRS-induced alterations in pituitary function include activation of the hypothalamic-pituitary adrenal (HPA) axis causing hypercortisolemia, the euthyroid sick syndrome, and cessation of reproductive function. These changes are in part mediated by cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1). IL-1 function depends on the local ratio of bioactive IL-1 and IL-1 receptor antagonist. Here we review our studies on IL-1 beta and IL-1ra mRNA levels in the pituitary in a rat model of SIRS. We have found that IL-1 beta mRNA peaked at 2 h after lipopolysaccharide (LPS) administration, increasing twelvefold over control values in the posterior pituitary and fivefold over controls in the anterior pituitary. IL-1ra mRNA levels peaked at 6 h post-LPS administration, later than those of IL-1 beta mRNA. IL-1ra mRNA levels increased tenfold in the anterior pituitary, but were induced only threefold in the posterior pituitary. IL-1ra gene expression is profoundly induced in the pituitary in vivo during systemic inflammation and its induction follows that of IL-1 beta, but it is differentially regulated and tissue-specific, occurring predominantly in the anterior pituitary. Future studies of the effects of IL-1 in the pituitary should take into account the local levels of IL-1ra.
Licinio
J
J
Clinical Neuroendocrinology Branch, Intramural Research Program, NIMH, NIH, Bethesda, Maryland 20892-1284, USA.
Wong
M L
ML
D000818:Animals; D003720:Densitometry; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010902:Pituitary Gland / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D013577:Syndrome
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012795:Sialoglycoproteins