EFFECTS OF INDOMETHACIN ON LIPOPOLYSACCHARIDE-INDUCED PLASMA PGE(2) CONCENTRATIONS AND CLINICAL-PATHOLOGICAL DISORDERS IN EXPERIMENTAL ENDOTOXEMIA

The effects of indomethacin, a cyclooxygenase inhibitor upon plasma co ncentrations of prostaglandin E-2 (PGE(2)), the febrile response,and m etabolic and hematological alterations induced by lipopolysaccharide ( LPS) were studied. Experimental endotoxemia was provoked via ip inject ion of 1.0 mg E coli LPS/kg in rats (group A). Indomethacin was introd uced/os (2.5 mg/kg) 30 min prior to LPS challenge (group B). Pretreatm ent with this medication completely inhibited the hyperthermic respons e to LPS and eliminated the LPS-induced non-specific symptoms of anore xia, adipsia, reduced locomotory activity and gastrointestinal trouble s. Plasma PGE(2) concentrations increased as early as the 2nd h after the LPS challenge but were blocked when endotoxin application was prec eded by indomethacin treatment. Indomethacin did not significantly inf luence hematological parameters. The dynamics of hematocrit and erythr ocyte counts were similar in both groups with a decrease up to the 2nd h followed by an increase to maximum at post-treatment day 3. Pretrea tment with indomethacin did not influence the endotoxin-induced leukop enia observed at the 2nd h or the accompanying neutropenia and left sh ift. Cyclooxygenase inhibition affected total protein concentrations; they were decreased in the early hours of the study (hours 4-6) in bot h groups. The later tendency towards Increase in total protein concent rations was more expressed in animals from group B. Changes in blood g lucose were characterized by a permanent tendency towards decrease aft er hour 2 of LPS challenge up to day 6 (group A). In group B, a simila r tendency was observed, but glucose concentrations decreased between hours 2-6 and then returned to initial values.