Thalidomide treatment modulates macrophage pro-inflammatory function and cytokine levels in Klebsiella pneumoniae B5055 induced pneumonia in BALB/c mice.

Abstract

Lung innate immune response plays an important role in the clearance of pathogens from lungs, however, profound activation of innate immune cells (alveolar macrophages or neutrophils) can lead to development of acute lung inflammation or injury by producing various pro-inflammatory molecules (IL-1, TNF-alpha and H2O2 etc.). Present study is designed to investigate the immunomodulatory action of thalidomide in Klebsiella pneumoniae B5055 induced acute lung infection in BALB/c mice. Acute lung inflammation was induced by intranasal instillation of K. pneumoniae B5055 into mice without any anaesthesia and treated with thalidomide (30 mg/kg/day/po) or normal saline orally using a treatment schedule shown to modulate pro-inflammatory innate immune response. Thalidomide treatment modulated pro-inflammatory function of alveolar macrophages by significantly (p<0.05) decreasing their phagocytic potential in terms of phagocytic uptake and intracellular killing, spreading and hydrogen peroxide (H2O2) release. Besides that thalidomide treatment also significantly (p<0.05) decreased neutrophil infiltration into the lung alveoli. Remarkably, the levels of pro-inflammatory cytokines (IL-1alpha and TNF-alpha) were found to be decreased significantly (p<0.05) in thalidomide treated group but the levels of IL-10 were found to be significantly (p<0.05) elevated. Thus thalidomide proved a promising immunomodulatory agent in acute lung inflammation associated with pneumonia caused by gram negative bacterial infection.

• Authors: Vijay Kumar, Kusum Harjai, Sanjay Chhibber
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 10 Issue 7 Pg. 777-83 (Jul 2010) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 20399910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Inflammation Mediators
• Thalidomide

Topics

• Animals
• Cells, Cultured
• Cytokines (genetics, immunology, metabolism)
• Inflammation Mediators (metabolism)
• Klebsiella Infections (drug therapy, immunology)
• Klebsiella pneumoniae (immunology, pathogenicity)
• Lung (pathology)
• Macrophages, Alveolar (drug effects, immunology, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Neutrophil Infiltration (drug effects)
• Phagocytosis (drug effects)
• Pneumonia (drug therapy, immunology)
• Thalidomide (administration & dosage, therapeutic use)