UP REGULATION OF NIACINE RECEPTOR IN MOUSE MACROPHAGES BY IN VIVO LPS INOCULATION. POTENTIAL ROLE IN LPS-INDUCED ENDOTOXIC SHOCK.

ZORRILLA ZUBILETE M; CREMASCHI G; GENARO A M; WALD MR; LIPSZYC P

Rosario, Santa Fe

Congreso; XLI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE).; 2009

Sociedad Argentina de Farmacología Experimental

Niacin is known to improve lipid metabolism and exert antioxidant/anti-inflammatory actions. The tissue damage that occurs during sepsis is largely mediated by macrophages. Our aim was to investigate if niacin may improve the evolution of LPS-induced septic shock. Moreover the participation of macrophage niacin receptor and pro-inflammatory cytokine production was also analyzed. To this end, C57Bl/6 mice were randomly assigned to niacin-treated (250 mg/Kg/day in drinking water) and untreated groups. Animals began the treatment 24h before the LPS (500 ug/mice) inoculation and continued until the end of the experiment and the survival was determined. Our results indicated that niacin-treated mice showed an increase in survival after endotoxic shock induction. The characterization of niacin receptor in macrophage by binding with [3H]-nicotinic acid showed an increase in the receptor number in macrophages from LPS-treated mice. Macrophages of normal animals stimulated in vitro with LPS showed an increase of IL-6 and TNF-alpha production, but not of IFN-gamma Addition of niacin did not modify cytokine production. It is probably that in vivo LPS induce INF-gamma production by T-lymphocyte that in turn induces up regulation of niacin receptors in macrophage. Under in vivo condition the regulation of pro-inflammatory cytokine production in macrophages by niacin could be possible. The involvement of this cytokine network is now under study.