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Infection and Immunity, April 2001, p. 2099-2106, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2099-2106.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Critical Role of CD14 for Production of Proinflammatory Cytokines and Cytokine Inhibitors during Sepsis with Failure To Alter Morbidity or Mortality

Samuel J. Ebong,1 Sanna M. Goyert,2 Jean A. Nemzek,1 Jiyoun Kim,1 Gerald L. Bolgos,1 and Daniel G. Remick1,*

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602,1 and North Shore University Hospital/New York University School of Medicine, Manhasset, New York 110302

Received 30 October 2000/Returned for modification 22 November 2000/Accepted 22 December 2000

We investigated the immunopathophysiologic responses during sepsis induced by cecal ligation and puncture (CLP) in CD4-deficient (CD14 knockout [CD14KO]) mice. Our studies were designed to specifically test the role of CD14 in the inflammatory response to sepsis and to ascertain if alterations would improve morbidity or mortality. Sepsis was induced using the CLP model with appropriate antibiotic treatment. The severity of sepsis increased in the CD14KO mice with increasing puncture size (18 gauge [18G], 21G, and 25G). Following CLP, body temperature (at 12 h) and gross motor activity levels of the sham and 25G CLP groups recovered to normal, while the 21G and 18G CLP groups exhibited severe hypothermia coupled with decreased gross motor activity and body weight. There were no significant differences in survival, temperature, body weight, or activity levels between CD14KO and control mice after 21G CLP. However, CD14KO mice expressed two- to fourfold less pro-inflammatory (interleukin-1beta [IL-1beta ], tumor necrosis factor [TNF], and IL-6) and anti-inflammatory (IL-10, IL-1 receptor antagonist, and TNF receptors I and II) cytokines in the blood after 21G CLP. Plasma levels of the chemokines macrophage inflammatory protein 2alpha and KC were similarly reduced in CD14KO mice. A similar trend of decreased cytokine and cytokine inhibitor levels was observed in the peritoneal cavity of CD14KO mice. Our results indicate that the CD14 pathway of activation plays a critical role in the production of both pro-inflammatory cytokines and cytokine inhibitors but has minimal impact on the morbidity or mortality induced by the CLP model of sepsis.

* Corresponding author. Mailing address: M2210 Med Sci I, 1301 Catherine Rd., Ann Arbor, MI 48109-0602. Phone: (734) 763-6454. Fax: (734) 763-6476. E-mail: remickd{at}umich.edu.

Infection and Immunity, April 2001, p. 2099-2106, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2099-2106.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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