Effects of antiinflammatory agents on chronic Salmonella typhimurium infection in a mouse model

Anti-inflammatory corticosteroids have been demonstrated to lower the resistance of the host to a range of infections in several different animal models. We have adapted the mouse model for Salmonella typhimurium infection, using a subcutaneous inoculation of 10(4) organisms in CBA/Ca mice. The chronic infection was potentiated by treatment with hydrocortisone given orally in the diet for up to 4 weeks, beginning on day 30 after infection. A dose of 25 mg/kg of body weight resulted in 100% mortality from Salmonella infection within 24 days of beginning hydrocortisone treatment. Nonsteroid drugs, indomethacin and a trial agent BW 755C, were compared with the corticosteroid in this model. No mortality was recorded during the 4 weeks of drug treatment in these groups. Fecal samples were monitored weekly, and drug-related effects on the normal fecal flora were observed. The kinetics of S. typhimurium infection were followed in both fecal and organ samples for the duration of the experiments. The model is useful for the determination of the lowered resistance of the host to infection after drug treatment and specifically demonstrated here the potential of the trial drug BW 755C as an active anti-inflammatory agent without one of the undesirable side effects of corticosteroids.