Protection against pulmonary infection with Klebsiella pneumoniae in mice by interferon-gamma through activation of phagocytic cells and stimulation of production of other cytokines

The study was designed to determine the role of interferon (IFN)-gamma in i nflammatory responses against experimentally induced pneumonia caused by Kl ebsiella pneumoniae. The host immunological responses in IFN-gamma gene kno ckout (IFN-gamma (-/-)) mice and immunocompetent control mice were compared . K. pneumoniae strain T-113 was inoculated intranasally into anaesthetised mice to induce pneumonia. Infected control mice survived significantly lon ger than infected IFN-gamma (-/-) mice. Viable bacterial counts in lungs an d blood abruptly increased in IFN-gamma (-/-) mice; in contrast, a gradual decrease in the number of bacteria was noted in control mice. During the ea rly stages of infection, the concentrations of interleukin (IL)-1 beta and IL-6 in broncho-alveolar lavage fluid and IL-1 beta in serum of IFN-gamma ( -/-) mice were significantly lower than in control mice. During the late st age of infection, serum IL-6 level in IFN-gamma (-/-) mice was significantl y higher than in control mice. These results suggest that the defective imm unological host response, including inflammatory cytokine production caused by deficiency of IFN-gamma, is one of the mechanisms that allow the progre ssion of pulmonary infection to systemic septicaemia.