Kupffer cells (KC) represent 15% of the liver cell population. During septic conditions, KC are the most important source of the cytokines (e.g. TNF-, IL-1 and IL-6) in the body. LPS-treatment (1mg/kg body weight) alters the number and functions of peroxisomes especially oxidation of saturated very long chain fatty acids, fatty acid that accumulate in pathognomonic amounts in X-linked adrenoleukodystrophy. Therefore, to investigate the possible role of kupffer cells in LPS-induced modulation of peroxisomal functions we studied the effect of endotoxin (LPS) on the expression of liver peroxisomalβ-oxidation enzymes in rats pretreated with gadolinium chloride (GAL) or LPS alone. Gadolinium chloride treatment produces inactivation/elimination of KC. Rats were treated with an i.v. injection of Gal (10 mg/kg body weight) 24 hrs before LPS treatment (i.p., 1 mg/kg body weight). Rats were sacrificed 18 hrs after LPS injection and subcellular organelles were prepared by differential and isopyenic density gradient centrifugation. Purity of the subcellular fractions was confirmed by their marker enzyme activites. The expression of catalase, acyl-CoA oxidase and thiolase in purified peroxisomes was analyzed by Westernblot analysis. In spite of approximately 50% reduction in the number of peroxisomes in liver of LPS-treated rat, the amount of peroxisomal β-oxidation enzymes (acyl-CoA oxidase and acyl-CoA thiolase) and catalase increased significantly in the remaining peroxisomes in LPS treated rats, but no such increase in these proteins was observed in livers of rats treated with Gal prior to LPS-treatment. These results show that KC secreted mediators are involved in the modulation of the expression of peroxisomal β-oxidation enzymes and their functions (Funded by grants from N.I.H. NS-22576).