Treatment of murine macrophages with murine interferon-gamma and tumour necrosis factor-alpha enhances uptake and intracellular killing of Pseudomonas aeruginosa

Abstract

SUMMARY Murine interferon-gamma (MuIFN-γ) and murine tumour necrosis-alpha (MuTNF-α) are known to be potent immunomodulators of several aspects of the immune response, and they have been shown to exert profound effects on macrophages and monocytcs. The purpose of this study was to determine the effects of MuIFN-γ and MuTNF-α on the phagocytosis (uptake and intracellular killing) of opsonized Pseudomonas aeruginosa. Unstimulated peritoneal macrophages obtained from CBA/c mice were exposed to different concentrations ol'recombinant forms of ihecytokines (rMuIFN-γ and rMuTNF-α) for different periods of time. Phagocytosis was assayed using different concentrations of opsonized Ps. aeruginosa. In all cases the pretreatment of the cells with the cytokines increased significantly the uptake and the intracellular killing of bacteria in a dose-dependent manner. rMuTNF-α was effective only at 1000 U/ml. Combined treatment with the cytokines showed a less than additive effect with rMuIFN-γ and rMuTNF-α at concentrations of 10 U/ml and 100 U/ml. In the in vivo experiments, peritoneal macrophages obtained from rMuIFN-γ- or rMuTNF-α-treated mice showed enhancement of the intracellular killing of opsonized bacteria in a dose-dependent manner.