The Effect of Etanercept on Hepcidin Gene Expression and Iron Profile in a Rat Model of Anemia of Chronic Inflammation

Maha Safwat Abdel Rahman Elsheemy


Background &Aim:Anemia of chronic inflammation (ACI)complicates chronic inflammatory conditions.Hepcidin synthesis and release is substantially provoked by inflammatory cytokines generated from chronic inflammation such as RA.RA is associated with increased levels of TNFα and presents with ACI. The present study investigated the effect of etanercept as an anti TNFαon hepcidin expression and anemia progression in animal model of ACI. Method: Four groups of male Wister rats (8 per group) were designed;Normal control group, FCA group (paw injection with1 mg of heat-inactive Mycobacterium bovisin 0.1 ml paraffin oil repeated twice after one month with ten days interval), Etanercept group; (0.3 mg/kg 3 times/ week for 3 weeks S.C) in naïve rats and FCA/Etanercept group (received FCA as inFCA group) and treatedwith etanercept (as in etanercept group). Etanercept treatment started from day 40 day to day 60 from the start of the experiment. Results:FCA injections resulted at the end of the study in significant weight loss, both paws swelling together with decrease in Hb level and RBCs indices and iron profile confirming the establishment of arthritis with anemia. This was accompanied by tripling of serum TNFα level and provoking significant increase in hepcidin gene expression. Etanercept subcutaneous injection in naïve animals for three weeks resulted in a significant prevention of the natural weight gain and natural increase in the hemoglobin level without causing anemia together with increasing the MCV in comparison to the control animals. Besides, etanercept caused significant increase in serum iron and decrease in ferritin level. These findings were associated with affection of the hepcidin expression towards the increase, which did not reach statistical significance.Administration of etanercept for 3 weeks in FCA injected animals resulted insignificant weight loss withmarked improvement of paw swelling. Additionally, treatmentwith etanercept resulted in correction of Hblevel, MCV and MCHand restoration of serum iron and ferritin, both to above the normal levels.TNFα level was lowered to about half its value after treatment with etanercept in comparison to the level recorded in untreated FCA group. Significant reduction occurred in hepcidin expression with etanercept treatment in comparison to untreated FCA animals. Conclusion:FCA-rats treated with etanercept exhibited a reduction in hepcidin expression with subsequent improvement in Hb, RBCs indices and iron profile. That could be explained in part by the amelioration of the inflammation rather than a direct effect of etanercept as an anti TNF-α. Key words: Hepcidin; Iron; TNFα; Anemia; Etanercept; Rheumatoid Arthritis.

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Other Titles تأثير ايتانيرسيبتعلى التعبيرالجينيللهيبسيدين و صورة الحديد في نموذج جرذان لفقر دم الإلتهاب المزمن
Issue Date 2015

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