Reduction by Cefodizime of the Pulmonary Inflammatory Response Induced by Heat-Killed Streptococcus pneumoniae in Mice
AUTOR(ES)
Bergeron, Yves
FONTE
American Society for Microbiology
RESUMO
It has recently become apparent that overwhelming inflammatory reactions contribute to the high mortality rate associated with pneumococcal infection in immunocompetent hosts. Cefodizime (CEF) is an antibiotic that seems to be endowed with immunomodulating properties. To investigate the influence of CEF on the pulmonary inflammatory response induced by Streptococcus pneumoniae, we infected mice with repeated intranasal inoculations of 107 CFU of heat-killed fluorescein isothiocyanate-labeled bacteria, which are insensitive to the killing properties of the drug. CEF downregulated but did not abolish the strong polymorphonuclear leukocyte (PMN) recruitment induced by S. pneumoniae. PMN recruitment was not primarily mediated by leukotriene B4 in this model. The drug did not interfere with intrinsic mechanisms of phagocytosis by PMNs and alveolar macrophages. CEF totally abrogated the pneumococcus-induced tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion in bronchoalveolar lavage fluid. The drug also prevented IL-6 release in lung homogenates and partly inhibited TNF-α, but it did not interfere with IL-1α secretion in the lungs of infected mice. The fractional and selective downregulation of inflammatory cells and cytokines by CEF suggests cell-specific and intracellular specific mechanisms of interaction of the drug. The immunomodulatory properties of CEF may help restrain excessive inflammatory reactions, thus contributing to the reported good clinical efficacy of the drug against lower respiratory tract infections.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=105879Documentos Relacionados
- Influence of Cefodizime on Pulmonary Inflammatory Response to Heat-Killed Klebsiella pneumoniae in Mice
- Immunomodulating Effects of HMR 3004 on Pulmonary Inflammation Caused by Heat-Killed Streptococcus pneumoniae in Mice
- Erythromycin Inhibits Tumor Necrosis Factor Alpha and Interleukin 6 Production Induced by Heat-Killed Streptococcus pneumoniae in Whole Blood
- Analysis of immunization route-related variation in the immune response to heat-killed Salmonella typhimurium in mice.
- Direct activation of human peritoneal mesothelial cells by heat-killed microorganisms.