The role of cytokines in bacterial pneumonia: an inflammatory balancing act.

Bacterial pneumonia is a leading cause of morbidity and mortality in both developed and developing countries. While tremendous advances have been made in the treatment of pneumonia using broad-spectrum antibiotic regimens, these approaches have resulted in the recent emergence of multidrug resistant bacteria. To understand better the role of the host immune response to pulmonary bacterial infections, several in vivo animal models have been developed using different bacterial agents: two acute infection models using Klebsiella pneumoniae and Streptococcus pneumoniae and one model of chronic infection using Pseudomonas aeruginosa. To summarize, the resolution of pulmonary bacterial infections involves a finely orchestrated balancing act of proinflammatory and antiinflammatory cytokines. On initial encounter with deposited bacteria, resident alveolar macrophages become activated and secrete proinflammatory cytokines and chemokines, resulting in the eventual generation of a proinflammatory amplification loop between resident or recruited macrophages or polymorphonuclear neutrophils and lymphocytes. As the infection is cleared, a second wave of antiinflammatory cytokines is produced to localize the inflammatory response to within the lung microenvironment and eventually to downmodulate this response. Experimental perturbation of the host inflammatory "cycle" can have either beneficial or detrimental effects on bacterial clearance. With this in mind, a cautionary approach needs to be used in proposing immunoadjuvant therapies for pneumonia treatment.