Potentiation of indomethacin-induced anti-inflammatory response by montelukast in formalin-induced inflammation in rats

The leukotrienes and prostaglandins are biologically active metabolites derived from arachidonic acid. The leukotrienes have a role in inflammatory diseases such as allergic rhinitis, inflammatory bowel disease and asthma. Montelukast, a cysteinyl leukotriene receptor antagonist, is claimed to be effective in asthma. The present study aimed to assess the role of cysteinyl leukotriene receptor antagonist on peripheral inflammation and whether montelukast treatment enhances the anti-inflammatory effect of indomethacin. Anti-inflammatory response was measured using a plethysmometer. Histopathologic examination for leukocyte accumulation was done. Montelukast (0.5-2mg/kg, i.p.) produced a significant anti-inflammatory effect in dose dependent manner against formalin-induced rat paw oedema at 1h but not in 3 and 5 h. When indomethacin (5 mg/kg, i.p) was co-administered with montelukast (1 mg/kg, i.p), the anti-inflammatory effects of indomethacin were significantly increased as compared to the per se effect at 3 and 5 hour after formalin challenge. In histopathology it has been found that combination therapy significantly decreased migration of leucocytes into the site of inflammation. These results show that montelukast has anti-inflammatory properties in peripheral tissue and markedly potentiates the anti-inflammatory activity of indomethacin at 3 and 5 h. It is expected that combination of montelukast with cyclooxygenase inhibitor would prove to be a novel approach to manage complex inflammatory conditions.