Neutralization of TNFα alters inflammation in guinea pig tuberculous pleuritis

Previously, treatment with anti-gpTNFα antibody enhanced TNFα 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-gpTNFα or normal serum control. Neutralizing TNFα 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-gpTNFα antibody. Cells from the pleural exudate in both treatment groups at day 3 expressed predominantly TNFα and IFNγ mRNA. By day 5, treatment with anti-gpTNFα antibody significantly reduced TNFα mRNA and increased TGFβ and iNOS mRNA expression, a transition which did not occur in the control group until day 8. TNFα mRNA overwhelmed the cytokine milieu of microdissected pleural granulomas in the control group at day 3 whereas TNFα, IFNγ, and TGFβ mRNA dominated the anti-gpTNFα-treated group. At day 8, granulomas from the control group began shifting towards an anti-inflammatory profile with increased levels of TGFβ mRNA. Neutralization of TNFα hastened the transition to an anti-inflammatory cytokine response in guinea pig pleural granulomas and exudate cells.