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|Title:||The Yin-Yang of TNF⍺ in the guinea pig model of tuberculosis|
|Authors:||Ly, Lan H|
McMurray, David N
|Abstract:||Tumour necrosis factor alpha (TNF-⍺) is a prototypic pro-inflammatory cytokine that has a central role in the initial host response to Mycobacterium tuberculosis infection. It is a key player in granuloma formation, macrophage activation, bacterial killing, and pathology in vivo. However, the exact mechanism has not been completely understood. This review summarizes the TNFa data acquired from the ‘gold standard’ guinea pig animal model of tuberculosis. While production of TNF⍺ is widely accepted as beneficial to the host response, we have found that this hypothesis is just one side of the story. TNF⍺ can up-regulate and down-regulate some key pro-inflammatory cytokines (IFNg, IL-12p40) and differentially modulate macrophage activation and intracellular bacterial growth. Neutralization of TNF⍺ in vivo allows an anti-inflammatory TGFb-mediated response to develop. Furthermore, BCG vaccination modulates TNF⍺ responses directly in the pulmonary granulomas to reduce tissue damage. The bipolar nature of TNF⍺ should be considered as knowledge of this critical molecule continues to grow.|
|Appears in Collections:||IJEB Vol.47(06) [June 2009]|
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