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.

Models of Inflammation: Carrageenan Air Pouch

“…Both drugs decrease number of leukocytes in pouch exudate; dexamethasone also inhibits TNF levels in exudate, whereas effects of indomethacin on TNF levels are variable Romano et al, 1997;Mattei et al, 2015;Vigil et al, 2008 Etanercept (5 mg/kg, i.p. )…”

“…Decreases number of leukocytes and levels of TNF in pouch exudate Mattei et al, 2015 Tacrolimus (2-5 mg/kg, p.o. )…”

Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

“…However, such treatment has been associated with various unexpected effects such as infection, allergic reaction, malignancy or confounding results (Bhatia et al ., 2016) and may affect other important body functions such as development, homeostasis, metabolism and cognition (Biddie et al ., 2012). In addition, Tumour necrosis factor-α (TNF-α) antagonists, such as rituximab, adalimumab, thalidomide and etanercept have been utilised to treat inflammation and TNF-α-mediated chronic pain during the onset of inflammation, sensory nerve damage and autoimmune diseases (Feldmann and Maini, 2003; Leung and Cahill, 2010; Mattei et al ., 2015). Nevertheless, the safety of these TNF-α antagonists has raised severe concerns in various medical situations (Isyar et al ., 2015; Kübra Elçioğlu et al ., 2015; Lories and de Vlam, 2014).…”

Hydroxylated Fullerene: A Stellar Nanomedicine to Treat Lumbar Radiculopathy via Antagonizing TNF-α-Induced Ion Channel Activation, Calcium Signaling, and Neuropeptide Production

“…11,12 TNF-α antagonists have emerged as a new therapy to treat inflammation-related chronic pain and sensory nerve damage. 13–15 However, a series of safety concerns have been raised regarding these TNF-α antagonists. 16–18 Therefore, there is an urgent medical need to discover a safe and effective therapy to treat lumbar radiculopathy and discogenic low back pain.…”