Neutralization of TNF alpha alters inflammation in guinea pig tuberculous pleuritis

作者：Ly Lan H^*; Jeevan Amminikutty; McMurray David N

来源：Microbes and Infection, 2009, 11(6-7): 680-688.

DOI：10.1016/j.micinf.2009.04.015

• Tuberculous pleurisy
• Guinea pig
• TNF alpha

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

• 出版日期2009-6