| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Physiology Program, Harvard School of Public Health, Boston, MA, USA
2 Center for Animal Resources and Comparative Medicine, Harvard Medical School, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: jmizgerd{at}hsph.harvard.edu.
During infection, inflammation is essential for host defense, but it can injure tissues and compromise organ function. TNF-
and IL-1 ( and 
) 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 E. 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 independent 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- and IL-1 decreases inflammation and preserves lung compliance.
This article has been cited by other articles:
|
|
 |
|
  L. J. Quinton, M. R. Jones, B. E. Robson, and J. P. Mizgerd Mechanisms of the Hepatic Acute-Phase Response during Bacterial Pneumonia Infect. Immun., June 1, 2009; 77(6): 2417 - 2426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, Y. Jia, M. Pichavant, F. Loison, B. Sarraj, A. Kasorn, J. You, B. E. Robson, D. T. Umetsu, J. P. Mizgerd, et al. Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia Blood, May 14, 2009; 113(20): 4930 - 4941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Kafka, E. Ling, G. Feldman, D. Benharroch, E. Voronov, N. Givon-Lavi, Y. Iwakura, R. Dagan, R. N. Apte, and Y. Mizrachi-Nebenzahl Contribution of IL-1 to resistance to Streptococcus pneumoniae infection Int. Immunol., September 1, 2008; 20(9): 1139 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Mizgerd and S. J. Skerrett Animal models of human pneumonia Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L387 - L398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Mizgerd Acute Lower Respiratory Tract Infection N. Engl. J. Med., February 14, 2008; 358(7): 716 - 727. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Elizur, T. L. Adair-Kirk, D. G. Kelley, G. L. Griffin, D. E. deMello, and R. M. Senior Tumor Necrosis Factor-{alpha} from Macrophages Enhances LPS-Induced Clara Cell Expression of Keratinocyte-Derived Chemokine Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 8 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Johnston, J. P. Mizgerd, L. Flynt, L. J. Quinton, E. S. Williams, and S. A. Shore Type I Interleukin-1 Receptor Is Required for Pulmonary Responses to Subacute Ozone Exposure in Mice Am. J. Respir. Cell Mol. Biol., October 1, 2007; 37(4): 477 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Fields, J. M. Bishai, W. Mitzner, and E. M. Wagner Effects of pulmonary ischemia on lung morphology Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L254 - L258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Prince, J. P. Mizgerd, J. Wiener-Kronish, and J. Bhattacharya Cell signaling underlying the pathophysiology of pneumonia Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L297 - L300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jeyaseelan, S. K. Young, M. Yamamoto, P. G. Arndt, S. Akira, J. K. Kolls, and G. S. Worthen Toll/IL-1R Domain-Containing Adaptor Protein (TIRAP) Is a Critical Mediator of Antibacterial Defense in the Lung against Klebsiella pneumoniae but Not Pseudomonas aeruginosa J. Immunol., July 1, 2006; 177(1): 538 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yano, P. C. Liaw, J. M. Mullington, S.-C. Shih, H. Okada, N. Bodyak, P. M. Kang, L. Toltl, B. Belikoff, J. Buras, et al. Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality J. Exp. Med., June 12, 2006; 203(6): 1447 - 1458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jeyaseelan, R. Manzer, S. K. Young, M. Yamamoto, S. Akira, R. J. Mason, and G. S. Worthen Toll-IL-1 Receptor Domain-Containing Adaptor Protein Is Critical for Early Lung Immune Responses against Escherichia coli Lipopolysaccharide and Viable Escherichia coli J. Immunol., December 1, 2005; 175(11): 7484 - 7495. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
