The role of NF-KB in the effect of fenofibrate on a mouse model of allergic asthma

Background/aim: Asthma is a chronic inflammatory disease of the airways that affects nearly 300 million people in the world. Asthma has a complex pathophysiology and about 5-10 % of patients are not fully responsive to the currently available treatments. The aim of this study is to investigate the involvement of NF-κB in the effects of fenofibrate on a mouse model of allergic asthma. Materials and methods: A total of 49 Balb/c mice were randomly distributed into 7 groups (n=7). Allergic asthma model was induced by administering intraperitoneal injections of ovalbumin, followed by provocation with inhaled ovalbumin. Fenofibrate was orally given in 3 different doses (1, 10 and 30 mg/kg) through days 21 to 30. On day 31, pulmonary function test using whole body plethysmography was performed. The mice were sacrificed 24 hours later. Blood samples were obtained, and serum of each sample was separated for IgE determination. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to measure IL-5 and IL-13. Nuclear extracts of lung tissues were employed to assess NF-κB p65 binding activity. Results: Penh values, IL-5 and IL-13 levels in BALF and lung tissues and IgE levels in serum were significantly increased in ovalbumin-sensitized and challenged mice. Administration of fenofibrate (10 and 30 mg/kg) demonstrated significantly lower Penh values. IL-13 levels in the BALF and lung tissues of FEN1 group were statistically significantly reduced. BALF and lung tissue IL-5 and IL-13 levels in mice treated with 10 and 30 mg/kg fenofibrate were statistically significantly diminished when compared to the OVA group. IgE levels in the serum of FEN30 group mice have shown a prominent reduction. NF-κB p65 binding activity was statistically significantly reduced in allergic mice treated with 30 mg/kg fenofibrate compared to mice sensitized and challenged with ovalbumin. Conclusions: The ameliorative effects of fenofibrate on airway inflammation and hyperreactivity may be due to its inhibition of NF-κB activity. Keywords: Allergic asthma, NF-κB, fenofibrate, ovalbumin, whole-body plethysmography.