ROLES OF THE SPLENIC CYTOKINES AND ARACHIDONIC-ACID METABOLITES IN SEVERE HEPATIC-INJURY AFTER LIPOPOLYSACCHARIDE INJECTION IN CHRONICALLY ALCOHOL-FED RATS

We examined the early changes after lipopolysaccharide (LPS) injection in chronically alcohol-fed rats with or without splenectomy. Administration of 2 mg/kg body weight LPS caused severe hepatic injury. The plasma aspartate aminotransferase (ASAT) activity was significantly higher in sham-operated rats 8 hr after LPS injection than in splenectomized rats. The plasma tumor necrosis factor (TNF) activity was also significantly higher 1 hr after LPS injection in sham-operated rats than in splenectomized rats. The plasma thromboxane (TX) B-2/6-keto-prostaglandin (PG) F-1 alpha ratio increased in sham-operated rats after LPS injection. Therefore, the balance of arachidonic acid metabolites was in a hypercoagulated state in sham-operated rats after the LPS injection. Neutrophil infiltration into liver tissue increased in sham-operated rats after the LPS injection. The cytokines and arachidonic acid metabolites released from the spleen after LPS injection in alcohol-fed rats may play important roles in severe hepatic injury.