Potentiation of murine cytomegalovirus pneumonitis by antibiotics in clinical use

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Abstract
Nineteen antibiotics were screened for their effects on the proliferation of murine spleen cells in vitro. Ketoconazole supressed lymphoproliferation at clinically-attainable concentrations, whilst tetracycline, cephalothin, rifampicin and ciprofloxacin were also inhibitory at relatively low concentrations. These antibiotics were selected for further study. High concentrations of cephalothin inhibited macrophage uptake of colloidal gold, while spleen cells from mice treated with ketoconazole responded poorly to mitogenic stimulation in vitro. Humoral responses to ovalbumin, polyvinylpyrrolidone and murine cytomegalovirus (MCMV) were not suppressed by oral administration of ketoconazole, tetracycline, cephalothin, rifampicin or ciprofloxacin to mice. However, MCMV-infected mice receiving these antibiotics had increased virus loads and a greater persistence of virus and interstitial pneumonitis in their lungs. This was observed with clinicallyattainable serum concentrations of cephalothin, tetracycline and ciprofloxacin. The findings warrant further investigation as the antibiotics are used to control secondary infections in immunosuppressed patients, many of whom experience cytomegalovirus disease.

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