Murine peritoneal macrophages were isolated by adherence and their listericidal activity assessed in the presence or absence of selected cytokines. Untreated macrophages were not highly listericidal, showing moderate killing in the first 2 h after infection, and allowed progressive microbial growth thereafter (up to 9 h). Pre-treatment of cells with 10 to 100 U/ml of IFN-gamma allowed macrophages to develop sustained listericidal activity for the 9-h observation period, with a 2-log reduction of Listeria CFU per monolayer. Pulsing of cells with TNF-alpha alone did not result in enhanced microbicidal activity but TNF-alpha potentiated IFN-gamma-induced listericidal activity, resulting in high levels of killing when both cytokines were present. Conversely, macrophages pre-treated with interleukin-3 (IL-3) or colony-stimulating factor-1 (CSF-1) were found to be much more permissive for Listeria growth. Neither IL-3 nor CSF-1 abrogated IFN-gamma-induced listericidal activity. Moreover, neither IL-3 nor CSF-1 had any effect on the ability of macrophages to develop a respiratory burst following Listeria infection, as judged by H2O2 release following in vitro infection. Overall, these results suggest that different cytokines may have opposing effects on intracellular microbial growth, and that the balance of cytokine production in vivo may determine the resistance or susceptibility of the infected host.
