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Neutralization of TNFalpha alters inflammation in guinea pig tuberculous pleuritis.

AbstractPreviously, treatment with anti-gpTNFalpha antibody enhanced TNFalpha mRNA expression in pulmonary granulomas microdissected from non-vaccinated guinea pigs, and modified splenic granuloma architecture. In this study, pleural fluid, cells, and granulomatous tissues were collected 3, 5, and 8 days post-pleurisy induction in guinea pigs treated with anti-gpTNFalpha or normal serum control. Neutralizing TNFalpha reduced the percentage of macrophages in the pleural exudate while increasing the proportions of neutrophils and lymphocytes. Cell-associated mycobacterial loads were increased in guinea pigs treated with anti-gpTNFalpha antibody. Cells from the pleural exudate in both treatment groups at day 3 expressed predominantly TNFalpha and IFNgamma mRNA. By day 5, treatment with anti-gpTNFalpha antibody significantly reduced TNFalpha mRNA and increased TGFbeta and iNOS mRNA expression, a transition which did not occur in the control group until day 8. TNFalpha mRNA overwhelmed the cytokine milieu of microdissected pleural granulomas in the control group at day 3 whereas TNFalpha, IFNgamma, and TGFbeta mRNA dominated the anti-gpTNFalpha-treated group. At day 8, granulomas from the control group began shifting towards an anti-inflammatory profile with increased levels of TGFbeta mRNA. Neutralization of TNFalpha hastened the transition to an anti-inflammatory cytokine response in guinea pig pleural granulomas and exudate cells.
AuthorsLan H Ly, Amminikutty Jeevan, David N McMurray (Affiliation: Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M Health Science Center, 463 Reynolds Medical Building, College Station, TX, USA. lhly at medicine.tamhsc.edu)
JournalMicrobes and infection / Institut Pasteur (Microbes Infect) 2009 May-Jun Vol. 11 Issue 6-7 Pg. 680-8 ISSN: 1769-714X [Electronic] France
PMID19389482 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Cytokines
  • Tumor Necrosis Factor-alpha
Topics
  • Animals
  • Cytokines (biosynthesis)
  • Exudates and Transudates (cytology)
  • Granuloma (immunology)
  • Guinea Pigs
  • Inflammation (pathology)
  • Macrophages (immunology)
  • Neutrophils (immunology)
  • T-Lymphocytes (immunology)
  • Tuberculosis, Pleural (immunology, pathology)
  • Tumor Necrosis Factor-alpha (antagonists & inhibitors)