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

Rheumatoid arthritis (RA) is one of several inflammatory and autoimmune diseases that affect approximately 1 % of world’s population. The development of TNF inhibitors in the last decade represents a great advance in the treatment of mild and severe forms of RA. Etanercept is one of these drugs that...

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Veröffentlicht in:Naunyn-Schmiedeberg's archives of pharmacology 2015-12, Vol.388 (12), p.1247-1257
Hauptverfasser: Mattei, Rodrigo Antônio, Dalmarco, Eduardo Monguilhott, Fröde, Tânia Silvia
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description Rheumatoid arthritis (RA) is one of several inflammatory and autoimmune diseases that affect approximately 1 % of world’s population. The development of TNF inhibitors in the last decade represents a great advance in the treatment of mild and severe forms of RA. Etanercept is one of these drugs that is useful for RA treatment, but the mechanism of inhibition of the signaling pathway of inflammation was not completely elucidated. This study was conducted to evaluate the anti-inflammatory effect of etanercept in comparison to reference drugs (dexamethasone and indomethacin). Inflammation was induced by subcutaneal administration of carrageenan in the Swiss albino mice using the murine air pouch model. Exudation; leukocytes; myeloperoxidase (MPO); adenosine deaminase (ADA); nitric oxide metabolites (NOx); tumor necrosis factor (TNF); interferon gamma (IFN-γ); interleukins (IL) IL-6, IL-17, IL-10, IL-4, and IL-2; nuclear transcription factor kappa B (NF-κB) activation and apoptosis were evaluated 24 h after the induction of inflammation. Treatment with etanercept significantly inhibited exudate concentrations; leukocyte count; MPO and ADA activities; NOx, TNF, IFN-γ, and IL-17 levels; and NF-kappa B activation ( p  
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The development of TNF inhibitors in the last decade represents a great advance in the treatment of mild and severe forms of RA. Etanercept is one of these drugs that is useful for RA treatment, but the mechanism of inhibition of the signaling pathway of inflammation was not completely elucidated. This study was conducted to evaluate the anti-inflammatory effect of etanercept in comparison to reference drugs (dexamethasone and indomethacin). Inflammation was induced by subcutaneal administration of carrageenan in the Swiss albino mice using the murine air pouch model. Exudation; leukocytes; myeloperoxidase (MPO); adenosine deaminase (ADA); nitric oxide metabolites (NOx); tumor necrosis factor (TNF); interferon gamma (IFN-γ); interleukins (IL) IL-6, IL-17, IL-10, IL-4, and IL-2; nuclear transcription factor kappa B (NF-κB) activation and apoptosis were evaluated 24 h after the induction of inflammation. Treatment with etanercept significantly inhibited exudate concentrations; leukocyte count; MPO and ADA activities; NOx, TNF, IFN-γ, and IL-17 levels; and NF-kappa B activation ( p  &lt; 0.05). Etanercept induced apoptosis, reducing the number of viable neutrophils without increasing necrosis ( p  &lt; 0.05). Our results suggest that the anti-inflammatory mechanism of action of etanercept may be via decrease of NF-κB activation. This effect promoted the reduction of pro-inflammatory cytokines and NOx and the induction of neutrophil apoptosis. 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subjects Animals
Apoptosis - drug effects
Apoptosis - physiology
Arthritis, Rheumatoid - chemically induced
Arthritis, Rheumatoid - drug therapy
Arthritis, Rheumatoid - metabolism
Biomedical and Life Sciences
Biomedicine
Carrageenan - toxicity
Disease Models, Animal
Etanercept - pharmacology
Etanercept - therapeutic use
Immunosuppressive Agents - pharmacology
Immunosuppressive Agents - therapeutic use
Inflammation - chemically induced
Inflammation - drug therapy
Inflammation - metabolism
Inflammation Mediators - antagonists & inhibitors
Inflammation Mediators - metabolism
Leukocytes - drug effects
Leukocytes - metabolism
Mice
Neurosciences
NF-kappa B - antagonists & inhibitors
NF-kappa B - metabolism
Original Article
Pharmacology/Toxicology
title Etanercept administration prevents the inflammatory response induced by carrageenan in the murine air pouch model
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