| Full text | |
| Author(s): |
Soares, Alexandre Learth
[1]
;
Coelho, Fernando Rodrigues
[1]
;
Guabiraba, Rodrigo
[2, 3]
;
Kamal, Mamdouh
[2, 3]
;
Boris Vargaftig, B.
[1]
;
Li, Lily
;
Li, Jian
[4]
;
Tavares-de-Lima, Wothan
[1]
;
Ryffel, Bernhard
[2, 3]
Total Authors: 9
|
| Affiliation: | [1] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, Sao Paulo - Brazil
[2] Univ Orleans, Lab Mol Immunol & Embryol, F-45071 Orleans - France
[3] CNRS, UMR 6218, F-45071 Orleans - France
[4] Centocor R&D, Dept Immunobiol, Horsham, PA - USA
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Shock; v. 34, n. 3, p. 306-313, SEP 2010. |
| Web of Science Citations: | 20 |
| Abstract | |
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. (AU) | |
| FAPESP's process: | 04/14128-0 - Neuroimmunomodulation: effects of drugs, stress and cytocines on central nervous and immune systems bidirectional relationships |
| Grantee: | João Palermo Neto |
| Support Opportunities: | Research Projects - Thematic Grants |