RENAL INTERLEUKIN-1 EXPRESSION DURING ENDOTOXEMIA AND GRAM-NEGATIVE SEPTICEMIA IN CONSCIOUS RATS

Endotoxin-induced cytokines such as interleukin-1 (IL-1) and tumor nec rosis factor (TNF) are thought to contribute to the proinflammatory ef fects of endotoxin in gram-negative infections. Using a conscious rat model of sepsis, induced by intravenous challenge with LD(95) doses of endotoxin (n = 24) or live Escherichia coli (E. coli) (n = 24), we ex amined frozen sections of kidney at various intervals for evidence of IL-1 alpha and TNF alpha expression. A transient glomerular endothelia l IL-1 alpha expression was demonstrated at 30 and 90 min after initia tion of the sepsis in both endotoxin and E. coli-treated animals using immunohistochemistry. The endothelial IL-1 alpha expression as determ ined by immunohistochemistry occurred at the same time as IL-1 alpha m RNA expression, as determined by Northern blot analysis. The glomerula r endothelial IL-1 alpha expression coincided with a slight but signif icant increase in the number of the glomerular polymorphonuclear leuko cytes as identified by naphthol AS-D chloroacetate esterase enzyme his tochemical reaction. Glomerular endothelial IL-1 alpha expression was virtually absent by 180 and 360 min. No TNF alpha expression was detec ted in the renal tissues at any time interval. Neither alpha-naphthyl acetate esterase-positive nor acid phosphatase-positive monocytes/macr ophages were identified in the glomeruli. Our findings provide direct in vivo evidence that the IL-1 alpha gene product is expressed locally in the kidney by glomerular endothelial cells in this septic rat mode l. (C) 1994 Wiley-Liss, Inc.