Effect of tumour necrosis factor-α receptor 1 genetic deletion on carrageenan-induced acute inflammation: a comparison with etanercept

Abstract

SummaryIn the present study, we used tumour necrosis factor-a receptor 1 knock-out mice (TNF-aR1KO) to evaluate an in vivo role of TNF-aR1 on the pathogenesis of inflammatory diseases. We used a murine model of carrageenaninduced acute inflammation (pleurisy), a preclinical model of airway inflammation. The data proved that TNF-aR1KO were resistant to carrageenan-induced acute inflammation compared with TNF-a wild-type mice. TNF-aR1KO 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-aR1KO at 4 h and 24 h after carrageenan injection. Moreover, TNF-a and interleukin-1b concentrations were reduced in inflamed areas and in pleural exudates from TNF-aR1KO. To support the results generated using pleural inflammation, carrageenaninduced paw oedema models were also performed. In order to elucidate whether the observed anti-inflammatory effects were related to the inhibition of TNF-a, we also investigated the effect of etanercept, a TNF-a 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 carrageenaninduced pleurisy. Our results showed that administration of etanercept resulted in the same outcome as that of deletion of the TNF-aR1 receptor, adding a new insight to TNF-a as an excellent target by therapeutic applications.

Etanercept administration prevents the inflammatory response induced by carrageenan in the murine air pouch model

“…These results are in accordance with the data reported by Mazzon et al (2008) who demonstrated that etanercept had an important antiinflammatory action by inhibiting the oxidative stress and some pro-inflammatory cytokines in a model of pleurisy induced by carrageenan in mice.…”

“…There are rare studies that focus on the antiinflammatory effect of etanercept concerning that described by Mazzon et al (2008) who demonstrated the effect of e t a n e r ce p t u p o n o x i d a t i v e s t r e s s ( ni t r i c o x i d e , myeloperoxidase) and upon some pro-inflammatory cytokines (TNF, IL-1β). This study focus on the first time the action of etanercept upon Th1/Th2/Th17 immune response and neutrophils apoptosis using an experimental model of arthritis.…”

Systemic changes following carrageenan-induced paw inflammation in rats

“…On the other hand, it is also known that carrageenan induces the synthesis of proinflammatory cytokines as it was demonstrated in experimental animals. Mazzon et al [26] described that a carrageenan injection causes a significant increase in TNFa and IL-1b in the pleural exudate and lung tissues in a carrageenan-induced pleurisy model in mice. TNFa and IL1b contribute to propagate local or systemic inflammatory processes [27,28].…”

Icariin Derivative Inhibits Inflammation through Suppression of p38 Mitogen-Activated Protein Kinase and Nuclear Factor-.KAPPA.B Pathways

“…Mazzon et al revealed that carrageenan injection caused a significant increase in TNF-a and IL-1b production, which help to propagate the extension of the local inflammatory process. 42) In addition, iNOS and COX-2 were also induced in inflammation progress; the iNOS and COX-2 pathways appear to operate together to maintain an inflammatory response by influencing blood flow and microvascular permeability.…”