Tumor necrosis factor is not associated with intestinal ischemia/reperfusion-induced lung inflammation. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Shock Année : 2010

Tumor necrosis factor is not associated with intestinal ischemia/reperfusion-induced lung inflammation.

Résumé

Intestinal ischemia-reperfusion (I/R) injury may cause acute systemic and lung inflammation. Here, we revisited the role of TNF-alpha in an intestinal I/R model in mice, showing that this cytokine is not required for the local and remote inflammatory response upon intestinal I/R injury using neutralizing TNF-alpha antibodies and TNF ligand-deficient mice. We demonstrate increased neutrophil recruitment in the lung as assessed by myeloperoxidase activity and augmented IL-6, granulocyte colony-stimulating factor, and KC levels, whereas TNF-alpha levels in serum were not increased and only minimally elevated in intestine and lung upon intestinal I/R injury. Importantly, TNF-alpha antibody neutralization neither diminished neutrophil recruitment nor any of the cytokines and chemokines evaluated. In addition, the inflammatory response was not abrogated in TNF and TNF receptors 1 and 2-deficient mice. However, in view of the damage on the intestinal barrier upon intestinal I/R with systemic bacterial translocation, we asked whether Toll-like receptor (TLR) activation is driving the inflammatory response. In fact, the inflammatory lung response is dramatically reduced in TLR2/4-deficient mice, confirming an important role of TLR receptor signaling causing the inflammatory lung response. In conclusion, endogenous TNF-alpha is not or minimally elevated and plays no role as a mediator for the inflammatory response upon ischemic tissue injury. By contrast, TLR2/4 signaling induces an orchestrated cytokine/chemokine response leading to local and remote pulmonary inflammation, and therefore disruption of TLR signaling may represent an alternative therapeutic target.

Domaines

Immunologie

Dates et versions

hal-00591498 , version 1 (09-05-2011)

Identifiants

Citer

Alexandre Learth Soares, Fernando Rodrigues Coelho, Rodrigo Guabiraba, Mamdouh Kamal, B Boris Vargaftig, et al.. Tumor necrosis factor is not associated with intestinal ischemia/reperfusion-induced lung inflammation.. Shock, 2010, 34 (3), pp.306-313. ⟨10.1097/SHK.0b013e3181cdc585⟩. ⟨hal-00591498⟩
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