Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia

M. J. Greenberger, R. M. Strieter, S. L. Kunkel, J. M. Danforth, R. E. Goodman, T. J. Standiford

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Abstract

Effective host defense against bacterial infection is dependent upon the vigorous recruitment and activation of neutrophils and macrophages. We hypothesized that IL-10 is produced in the setting of bacterial pneumonia, and this cytokine may attenuate host defense by inhibiting the expression of important activating and chemotactic cytokines. CD-1 mice were challenged with either 30 μl of saline or saline containing 103 CFUs of Klebsiella pneumoniae intratracheally (i.t.) and lungs were harvested at 8, 24, and 48 h. The i.t. inoculation with K. pneumoniae resulted in a 13-, 14-, and 8- fold increase in lung homogenate TNF, macrophage inflammatory protein-2 (MIP- 2), and macrophage inflammatory protein-1α (MIP-1α) levels, respectively, as compared with control animals. In addition, we observed an increase in IL- 10 mRNA and protein levels in lung homogenates, maximal at 48 h postinoculation. To establish the biologic relevance of IL-10 in Klebsiella pneumonia, we passively immunized CD-1 mice with 0.5 ml of rabbit anti- murine IL-10 serum or preimmune serum i.p. 2 h before i.t. administration of K. pneumoniae. Treatment of animals with anti-IL-10 serum resulted in increased levels of TNF, MIP-2, and MIP-1α, respectively, within lung homogenates at 24 and 48 h, as compared with preimmune-treated animals. Furthermore, neutralization of IL-10 resulted in a significant decrease in K. pneumoniae CFU in both lung homogenates and plasma harvested at 48 h, as well as a significant increase in survival in these animals. Our studies indicate that 1) IL-10 is produced during Klebsiella pneumonia; and 2) inhibition of IL-10 bioactivity in vivo results in enhanced bacterial clearance, increased expression of proinflammatory cytokines, and prolonged survival.

Original languageEnglish (US)
Pages (from-to)722-729
Number of pages8
JournalJournal of Immunology
Volume155
Issue number2
StatePublished - Jan 1 1995

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Greenberger, M. J., Strieter, R. M., Kunkel, S. L., Danforth, J. M., Goodman, R. E., & Standiford, T. J. (1995). Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia. Journal of Immunology, 155(2), 722-729.