title: Neutralization of TNFalpha alters inflammation in guinea pig tuberculous pleuritis.
abstract: Previously, 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.
authors.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@medicine.tamhsc.edu
authors.forename: Lan H
authors.initials: LH
authors.lastname: Ly
authors.forename: Amminikutty
authors.initials: A
authors.lastname: Jeevan
authors.forename: David N
authors.initials: DN
authors.lastname: McMurray
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005122:Exudates and Transudates / Q000166:cytology; D006099:Granuloma / Q000276:immunology; D006168:Guinea Pigs; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014396:Tuberculosis, Pleural / Q000276:immunology* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha