EFFECTS OF METHYL PALMITATE ON CYTOKINE RELEASE, LIVER-INJURY AND SURVIVAL IN MICE WITH SEPSIS

The effects of methyl palmitate (MP), a known inhibitor of Kupffer cel ls, were studied in a model of polymicrobial sepsis induced in CD-1 mi ce by cecal ligation and puncture (CLP). The inhibition of Kupffer cel ls by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) aft er lipopolysaccharide (LPS) challenge. The reduced activation of Kupff er cells resulted in lower levels of inflammatory products after CLP, TNF and IL-6 were significantly reduced in serum 2 h and 24 h respecti vely after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were signific antly reduced 8 and 24 h respectively after CLP. Liver toxicity was si gnificantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compare d with 3% in control mice. These findings suggest that Kupffer cells p lay an important role in liver damage and survival in sepsis.