Mucosal IL-12 is more effective than systemic IL-12 in augmenting IFN-γ expression and inhibiting allergic lung eosinophilia in murine lungs

S. Sur, B. K. Choudhury, J. S. Lam, P. Bouchard, J. S. Wild, N. Sur, R. Alam, A. Sigounas, D. Holbert, M. R. Van Scott

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The relative efficacy of mucosal (intratracheal) and systemic (intraperitoneal) delivery of interleukin (IL)-12 was evaluated in a mouse model of allergic lung eosinophilia. Mucosal administration of IL-12 achieved 100- to 600-fold higher bronchoalveolar lavage (BAL) levels of IL-12, but 2- to 10-fold lower serum levels compared to systemic administration. Whereas both mucosal and systemic IL-12 inhibited BAL eosinophil recruitment at high doses (100-1000 ng), only mucosal IL-12 was effective at low doses (1-10 ng). Mucosal, but not systemic, administration of 1000 ng of IL-12 increased interferon (IFN)-γ expression in BAL cells. In a model of ongoing eosinophilic inflammation, when mucosal or systemic IL-12 doses were initiated prior to peak eosinophilia, further eosinophil recruitment was inhibited. However, when IL-12 treatment was initiated after peak eosinophil recruitment occurred, recovery from eosinophilic inflammation was not facilitated. Our findings are the first to demonstrate that locally administered IL-12 inhibits eosinophil recruitment at 100-fold lower doses than systemic IL-12. The most likely mechanism of this enhanced inhibitory activity is a sustained increase in lung levels of IL-12 that augments IFN-γ production from BAL cells. We suggest that future studies should evaluate the efficacy of low doses of nebulized IL-12 in inhibiting eosinophilic lung inflammation in asthma.

Original languageEnglish (US)
Pages (from-to)457-476
Number of pages20
JournalExperimental Lung Research
Volume26
Issue number6
StatePublished - Jan 1 2000

Keywords

  • Asthma
  • Eosinophils
  • IFN-γ
  • IL-12
  • Th1
  • Th2

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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    Sur, S., Choudhury, B. K., Lam, J. S., Bouchard, P., Wild, J. S., Sur, N., Alam, R., Sigounas, A., Holbert, D., & Van Scott, M. R. (2000). Mucosal IL-12 is more effective than systemic IL-12 in augmenting IFN-γ expression and inhibiting allergic lung eosinophilia in murine lungs. Experimental Lung Research, 26(6), 457-476.