Elevated cAMP levels reverse Brucella melitensis-induced lipid peroxidation and stimulate IL-10 transcription in rats.

Brucella species are able to survive and replicate within the phagocytic vacuole of macrophages that induce chronic infection in humans and domestic animals. The activation of oxidative bactericidal activity is one of the defense systems which protect the host from the toxic effects of pathogens. The aim of this study was to evaluate lipid peroxidation, NO production, antioxidative system and inflammation during a period of brucella infection in a rat model; in addition to investigate the role of elevated intracellular cyclic AMP on Brucella-induced events. Brucella significantly induced lipid peroxidation in plasma, liver and spleen by 3-5-fold at 7 days postinfection. NO concentration was significantly elevated in the liver and spleen while unchanged in plasma. Cyclic AMP elevating agent, rolipram, administration (1mg/kg/day i.p., 3 days) gradually suppressed lipid peroxidation and NO formation to the basal level in plasma and spleen whilst only a slight decrease was observed in liver. Brucella considerably decreased SOD activity in the liver and spleen, with rolipram restoring the enzyme activity in liver and activity in spleen being unchanged. Reverse transcriptase PCR analyses showed that Brucella melitensis does not alter TNF-alpha and IFN-gamma transcriptions in liver and spleen. The pathogen did not consistently induce nitric oxide synthase mRNA transcriptions in animals; even in those housed in the same group. IL-10 transcription was induced by rolipram in spleen but not in liver. Our results suggest that activation of the cAMP/PKA pathway suppressed lipid peroxidation and the elevated NO concentrations caused by B. melitensis. Moreover, rolipram induced anti-inflammatory cytokine IL-10 transcription and SOD activity, albeit in a tissue dependent manner.