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Effect of tumour necrosis factor-alpha receptor 1 genetic deletion on carrageenan-induced acute inflammation: a comparison with etanercept.
Clin Exp Immunol. 2008 Jul; 153(1):136-49.CE

Abstract

In the present study, we used tumour necrosis factor-alpha receptor 1 knock-out mice (TNF-alphaR1KO) to evaluate an in vivo role of TNF-alphaR1 on the pathogenesis of inflammatory diseases. We used a murine model of carrageenan-induced acute inflammation (pleurisy), a preclinical model of airway inflammation. The data proved that TNF-alphaR1KO were resistant to carrageenan-induced acute inflammation compared with TNF-alpha wild-type mice. TNF-alphaR1KO showed a significant reduction in accumulation of pleural exudate and in the number of inflammatory cells, in lung infiltration of polymorphonuclear leucocytes and lipid peroxidation and showed a decreased production of nitrite/nitrate in pleural exudates. Furthermore, the intensity and degree of the adhesion molecule intercellular adhesion molecule-1 and P-selectin, Fas ligand (FasL), inducible nitric oxide sythase and nitrotyrosine determined by immunohistochemical analysis were reduced markedly in lung tissues from TNF-alphaR1KO at 4 h and 24 h after carrageenan injection. Moreover, TNF-alpha and interleukin-1beta concentrations were reduced in inflamed areas and in pleural exudates from TNF-alphaR1KO. To support the results generated using pleural inflammation, carrageenan-induced paw oedema models were also performed. In order to elucidate whether the observed anti-inflammatory effects were related to the inhibition of TNF-alpha, we also investigated the effect of etanercept, a TNF-alpha soluble receptor construct, on carrageenan-induced pleurisy. The treatment with etanercept (5 mg/kg subcutaneously 2 h before the carrageenan injection) reduces markedly both laboratory and histological signs of carrageenan-induced pleurisy. Our results showed that administration of etanercept resulted in the same outcome as that of deletion of the TNF-alphaR1 receptor, adding a new insight to TNF-alpha as an excellent target by therapeutic applications.

Authors+Show Affiliations

Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18505433

Citation

Mazzon, E, et al. "Effect of Tumour Necrosis Factor-alpha Receptor 1 Genetic Deletion On Carrageenan-induced Acute Inflammation: a Comparison With Etanercept." Clinical and Experimental Immunology, vol. 153, no. 1, 2008, pp. 136-49.
Mazzon E, Esposito E, Di Paola R, et al. Effect of tumour necrosis factor-alpha receptor 1 genetic deletion on carrageenan-induced acute inflammation: a comparison with etanercept. Clin Exp Immunol. 2008;153(1):136-49.
Mazzon, E., Esposito, E., Di Paola, R., Muià, C., Crisafulli, C., Genovese, T., Caminiti, R., Meli, R., Bramanti, P., & Cuzzocrea, S. (2008). Effect of tumour necrosis factor-alpha receptor 1 genetic deletion on carrageenan-induced acute inflammation: a comparison with etanercept. Clinical and Experimental Immunology, 153(1), 136-49. https://doi.org/10.1111/j.1365-2249.2008.03669.x
Mazzon E, et al. Effect of Tumour Necrosis Factor-alpha Receptor 1 Genetic Deletion On Carrageenan-induced Acute Inflammation: a Comparison With Etanercept. Clin Exp Immunol. 2008;153(1):136-49. PubMed PMID: 18505433.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of tumour necrosis factor-alpha receptor 1 genetic deletion on carrageenan-induced acute inflammation: a comparison with etanercept. AU - Mazzon,E, AU - Esposito,E, AU - Di Paola,R, AU - Muià,C, AU - Crisafulli,C, AU - Genovese,T, AU - Caminiti,R, AU - Meli,R, AU - Bramanti,P, AU - Cuzzocrea,S, Y1 - 2008/05/26/ PY - 2008/5/29/pubmed PY - 2008/7/26/medline PY - 2008/5/29/entrez SP - 136 EP - 49 JF - Clinical and experimental immunology JO - Clin Exp Immunol VL - 153 IS - 1 N2 - In the present study, we used tumour necrosis factor-alpha receptor 1 knock-out mice (TNF-alphaR1KO) to evaluate an in vivo role of TNF-alphaR1 on the pathogenesis of inflammatory diseases. We used a murine model of carrageenan-induced acute inflammation (pleurisy), a preclinical model of airway inflammation. The data proved that TNF-alphaR1KO were resistant to carrageenan-induced acute inflammation compared with TNF-alpha wild-type mice. TNF-alphaR1KO showed a significant reduction in accumulation of pleural exudate and in the number of inflammatory cells, in lung infiltration of polymorphonuclear leucocytes and lipid peroxidation and showed a decreased production of nitrite/nitrate in pleural exudates. Furthermore, the intensity and degree of the adhesion molecule intercellular adhesion molecule-1 and P-selectin, Fas ligand (FasL), inducible nitric oxide sythase and nitrotyrosine determined by immunohistochemical analysis were reduced markedly in lung tissues from TNF-alphaR1KO at 4 h and 24 h after carrageenan injection. Moreover, TNF-alpha and interleukin-1beta concentrations were reduced in inflamed areas and in pleural exudates from TNF-alphaR1KO. To support the results generated using pleural inflammation, carrageenan-induced paw oedema models were also performed. In order to elucidate whether the observed anti-inflammatory effects were related to the inhibition of TNF-alpha, we also investigated the effect of etanercept, a TNF-alpha soluble receptor construct, on carrageenan-induced pleurisy. The treatment with etanercept (5 mg/kg subcutaneously 2 h before the carrageenan injection) reduces markedly both laboratory and histological signs of carrageenan-induced pleurisy. Our results showed that administration of etanercept resulted in the same outcome as that of deletion of the TNF-alphaR1 receptor, adding a new insight to TNF-alpha as an excellent target by therapeutic applications. SN - 1365-2249 UR - https://www.unboundmedicine.com/medline/citation/18505433/Effect_of_tumour_necrosis_factor_alpha_receptor_1_genetic_deletion_on_carrageenan_induced_acute_inflammation:_a_comparison_with_etanercept_ L2 - https://doi.org/10.1111/j.1365-2249.2008.03669.x DB - PRIME DP - Unbound Medicine ER -