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Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct host responses.

Abstract：

OBJECTIVE:Pathogens that cause pneumonia may be treated in a targeted fashion by antibiotics, but if this therapy fails, then treatment involves only nonspecific supportive measures, independent of the inciting infection. The purpose of this study was to determine whether host response is similar after disparate infections with similar mortalities. DESIGN:Prospective, randomized controlled study. SETTING:Animal laboratory in a university medical center. INTERVENTIONS:Pneumonia was induced in FVB/N mice by either Streptococcus pneumoniae or two different concentrations of Pseudomonas aeruginosa. Plasma and bronchoalveolar lavage fluid from septic animals was assayed by a microarray immunoassay measuring 18 inflammatory mediators at multiple time points. MEASUREMENTS AND MAIN RESULTS:The host response was dependent on the causative organism as well as kinetics of mortality, but the pro-inflammatory and anti-inflammatory responses were independent of inoculum concentration or degree of bacteremia. Pneumonia caused by different concentrations of the same bacteria, Pseudomonas aeruginosa, also yielded distinct inflammatory responses; however, inflammatory mediator expression did not directly track the severity of infection. For all infections, the host response was compartmentalized, with markedly different concentrations of inflammatory mediators in the systemic circulation and the lungs. Hierarchical clustering analysis resulted in the identification of five distinct clusters of the host response to bacterial infection. Principal components analysis correlated pulmonary macrophage inflammatory peptide-2 and interleukin-10 with progression of infection, whereas elevated plasma tumor necrosis factor sr2 and macrophage chemotactic peptide-1 were indicative of fulminant disease with >90% mortality within 48 hrs. CONCLUSIONS:Septic mice have distinct local and systemic responses to Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia. Targeting specific host inflammatory responses induced by distinct bacterial infections could represent a potential therapeutic approach in the treatment of sepsis.

journal_name

Crit Care Med

journal_title

Critical care medicine

authors

McConnell KW,McDunn JE,Clark AT,Dunne WM,Dixon DJ,Turnbull IR,Dipasco PJ,Osberghaus WF,Sherman B,Martin JR,Walter MJ,Cobb JP,Buchman TG,Hotchkiss RS,Coopersmith CM

doi

10.1097/CCM.0b013e3181b4a76b

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

223-41

issue

eissn

0090-3493

issn

1530-0293

journal_volume

pub_type

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Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct host responses.