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

Soares, A.L., Coelho, F.R., Guabiraba, R., Kamal, M., Vargaftig, B.B., Li, L., Li, J., de-Lima, W.T. and Ryffel, B. (2010) Tumor necrosis factor is not associated with intestinal ischemia/reperfusion-induced lung inflammation. Shock, 34(3), pp. 306-313. (doi: 10.1097/SHK.0b013e3181cdc585)

Abstract

Intestinal ischemia-reperfusion (I/R) injury may cause acute systemic and lung inflammation. Here, we revisited the role of TNF-α 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-α 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-α levels in serum were not increased and only minimally elevated in intestine and lung upon intestinal I/R injury. Importantly, TNF-α 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-α 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Guabiraba Brito, Dr Rodrigo
• Authors: Soares, A.L., Coelho, F.R., Guabiraba, R., Kamal, M., Vargaftig, B.B., Li, L., Li, J., de-Lima, W.T., and Ryffel, B.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Shock
• ISSN: 1073-2322