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.