Roles for early response cytokines during Escherichia coli pneumonia revealed by mice with combined deficiencies of all signaling receptors for TNF and IL-1.
Publication/Presentation Date
6-1-2004
Abstract
During infection, inflammation is essential for host defense, but it can injure tissues and compromise organ function. TNF-alpha and IL-1 (alpha and beta) are early response cytokines that facilitate inflammation. To determine the roles of these cytokines with overlapping functions, we generated mice deficient in all of the three receptors mediating their effects (TNFR1, TNFR2, and IL-1RI). During Escherichia coli pneumonia, receptor deficiency decreased neutrophil recruitment and edema accumulation to half of the levels observed in wild-type mice. Thus these receptors contributed to maximal responses, but substantial inflammation progressed independently of them. Receptor deficiency compromised antibacterial efficacy for some infectious doses. Decreased ventilation during E. coli pneumonia was not affected by receptor deficiency. However, the loss of lung compliance during pneumonia was substantially attenuated by receptor deficiency. Thus during E. coli pneumonia in mice, the lack of signaling from TNF-alpha and IL-1 decreases inflammation and preserves lung compliance.
Volume
286
Issue
6
First Page
1302
Last Page
1310
ISSN
1040-0605
Published In/Presented At
Mizgerd, J. P., Lupa, M. M., Hjoberg, J., Vallone, J. C., Warren, H. B., Butler, J. P., & Silverman, E. S. (2004). Roles for early response cytokines during Escherichia coli pneumonia revealed by mice with combined deficiencies of all signaling receptors for TNF and IL-1. American journal of physiology. Lung cellular and molecular physiology, 286(6), L1302–L1310. https://doi.org/10.1152/ajplung.00353.2003
Disciplines
Medicine and Health Sciences
PubMedID
14966082
Department(s)
Department of Medicine
Document Type
Article