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

Abstract

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 < 0.05). Etanercept induced apoptosis, reducing the number of viable neutrophils without increasing necrosis (p < 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. The effect of etanercept upon neutrophils apoptosis may indicate the use of this drug therapy in the early stage of rheumatoid arthritis disease.

• Authors: Rodrigo Antônio Mattei, Eduardo Monguilhott Dalmarco, Tânia Silvia Fröde
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 388 Issue 12 Pg. 1247-57 (Dec 2015) ISSN: 1432-1912 [Electronic] Germany
• PMID: 26255064 (Publication Type: Journal Article)

Chemical References

• Immunosuppressive Agents
• Inflammation Mediators
• NF-kappa B
• Carrageenan
• Etanercept

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Arthritis, Rheumatoid (chemically induced, drug therapy, metabolism)
• Carrageenan (toxicity)
• Disease Models, Animal
• Etanercept (pharmacology, therapeutic use)
• Immunosuppressive Agents (pharmacology, therapeutic use)
• Inflammation (chemically induced, drug therapy, metabolism)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Leukocytes (drug effects, metabolism)
• Mice
• NF-kappa B (antagonists & inhibitors, metabolism)