title: Pneumonia-induced sepsis in mice: temporal study of inflammatory and cardiovascular parameters.
abstract: The aim of the present work is to provide a better comprehension of the pneumonia-induced sepsis model through temporal evaluation of several parameters, and thus identify the main factors that determine mortality in this model. Klebsiella pneumoniae was inoculated intratracheally in anesthetized Swiss male mice. Inflammatory and cardiovascular parameters were evaluated 6, 24 and 48 h after the insult. The results show that severity of infection and the mortality correlated with the amount of bacteria. Six, 24 and 48 h after inoculation, animals presented pathological changes in lungs, increase in cell number in the bronchoalveolar lavage, leukopenia, increase in TNF-α and IL-1β levels, hypotension and hyporesponsiveness to vasoconstrictors, the two latter characteristics of severe sepsis and septic shock. Significant numbers of bacteria in spleen and heart homogenates indicated infection spreading. Interestingly, NOS-2 expression appeared late after bacteria inoculation, whereas levels of NOS-1 and NOS-3 were unchanged. The high NOS-2 expression coincided with an exacerbated NO production in the infection focus and in plasma, as judging by nitrate + nitrite levels. This study shows that K. pneumoniae inoculation induces a systemic inflammatory response and cardiovascular alterations, which endures at least until 48 h. K. pneumoniae-induced lung infection is a clinically relevant animal model of sepsis and a better understanding of this model may help to increase the knowledge about sepsis pathophysiology.
authors: Department of Pharmacology, Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil.
authors: Regina
authors: R
authors: Sordi
authors: Octávio
authors: O
authors: Menezes-de-Lima
authors: Ana M
authors: AM
authors: Della-Justina
authors: Edir
authors: E
authors: Rezende
authors: Jamil
authors: J
authors: Assreuy
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007710:Klebsiella Infections / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D007711:Klebsiella pneumoniae / Q000276:immunology*; D007962:Leukocytes; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Klebsiella pneumoniae; NOS-2; mouse; nitric oxide; pneumonia; sepsis