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Septic shock and acute lung injury in rabbits with peritonitis: failure of the neutrophil response to localized infection.
Title | Septic shock and acute lung injury in rabbits with peritonitis: failure of the neutrophil response to localized infection. |
Publication Type | Journal Article |
Year of Publication | 2001 |
Authors | Matute-Bello, G, Frevert, CW, Kajikawa, O, Skerrett, SJ, Goodman, RB, Park, DR, Martin, TR |
Journal | Am J Respir Crit Care Med |
Volume | 163 |
Issue | 1 |
Pagination | 234-43 |
Date Published | 2001 Jan |
ISSN | 1073-449X |
Keywords | Animals, Body Fluids, Female, Neutrophils, Peritonitis, Rabbits, Respiratory Distress Syndrome, Adult, Shock, Septic |
Abstract | The major goal of this study was to investigate the mechanisms that link the host response to a local infection in the peritoneal cavity with the development of sepsis and lung injury. Rabbits were infected by intraperitoneal inoculation of fibrin clots containing Escherichia coli at 10(8), 10(9), or 10(10) cfu/clot. Physiologic, bacteriologic, and inflammatory responses were monitored, and the lungs were examined postmortem. At a dose of 10(8) cfu/clot the animals had resolving infection, and a dose of 10(9) cfu/clot resulted in persistent infection at 24 h, with minimal systemic manifestations. In contrast, inoculation of 10(10) cfu/clot resulted in rapidly lethal local infection, with septic shock and lung injury. The onset of septic shock was associated with a paradoxical lack of identifiable polymorphonuclear leukocytes (PMN; neutrophils) in the peritoneal cavity. The absence of PMN in the peritoneum was due in part to lysis of intraperitoneal PMN, because the peritoneal fluids contained free myeloperoxidase and induced rapid death of normal rabbit PMN in vitro. Although most animals became bacteremic, only those with a severe systemic inflammation response developed lung injury. These data show that control of an infection in the first compartment in which bacteria enter the host is a critical determinant of the systemic response. Above a threshold dose of bacteria, failure of the local neutrophil response is a key mechanism associated with deleterious systemic responses. Bacteremia alone is not sufficient to cause lung injury. Lung injury occurs only in the setting of a severe systemic inflammatory response and an inadequate leukocyte response at the primary site of infection. |
DOI | 10.1164/ajrccm.163.1.9909034 |
Alternate Journal | Am. J. Respir. Crit. Care Med. |
PubMed ID | 11208651 |
Grant List | AI 29103 / AI / NIAID NIH HHS / United States GM 37696 / GM / NIGMS NIH HHS / United States HL30542 / HL / NHLBI NIH HHS / United States |