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Female BALB/c and C3H/HeJ mice develop increased sensitivity to the toxic effects of indomethacin after injection of nonviable Corynebacterium parvum. The increased sensitivity developed within 4 days of intraperitoneal injection of the organisms and started to resolve 14 days after injection. The development of increased sensitivity was dependent on the quantity of organisms injected and the concentration of indomethacin utilized. The effect was not observed when C. parvum-treated animals were injected with aspirin. C. parvum-treated BALB/c mice also developed increased sensitivity to E. coli lipopolysaccharide (LPS). Although increased sensitivity to LPS and indomethacin paralleled each other in BALB/c mice, the experiments with the LPS-resistant C3H/HeJ mice indicated that the two phenomena could be separated. The pyridine extract residue of C. parvum was as effective as C. parvum whole cells in inducing indomethacin and LPS sensitivity. Therefore, activation of the reticuloendothelial system is probably a critical element in the induction of sensitivity to these agents.

Increased sensitivity of Corynebacterium parvum-treated mice to toxic effects of indomethacin and lipopolysaccharide