13-hydroxy-octadecatrienic acid (Hox alpha) ameliorates chronic murine colitis

Abstract

Introduction: ~he therapeutlc options for inflammatory bowel disease (IBD) remain limited, especially tor remission prolongation knti-TNF-a antibodies such as lntltxinmb are effective in the treatment ol flares but ohen lose their ethcacy with repetitive applications, 13Hydroxyoctadecatnen*~ acid a componem of the sungnig nettle leaf (Hox alpha, Strathmann (krrnany) reduces TNF-c~ secretion and is a known therapy m the setting of rheumatoid arthritis Aim: 1o investigate the etlect of Hox alpha on murine colitis disease activity in difli:rent colitic mouse models Methods: C3}tIHeJBir,IL-10-/and BALB/{ mice with DSSreduced acute and cbronic colitis were treated with 0 5mg/ml Hox alpha and compared to untreated controls Mice were clniically monitorvd and inflammation was assessed by histological scoring, analysis oi kcal/I.113 and measurement ot mucosal cytokine production by EL/SA Probkration of lynlphocytes ot the spleen and Peyers patches was quantified by 3H-thynlidine nico~)oration. Resuhs: Hox alpha-treated mice ,aqth chronic DSS colitis as well as Hox alpha-treated ID 10-A mice displayed signihcantly reduced clniical and histologB <al signs ot colitis than untreated mice (p<0 05) Fecal IL-113, mucosal IL-113 as well as TNF-~ concentrations were signit~cantly lowe* in Hox alpha-treated chronic DSS mice as well as in ttox alpha-treated lL-10-/mice m comparison with control rnice (p<0.05). Furthe*r~mre, 1ympbocyte prolfl~'ration postdipopolysaccharide stimulation was significantly reduced in Hox alpha-treated mice ( p < 0 0 0 1 ) Conclusions: The continuous use of Hox alpha is effective in the amelioration of chronic murme colitis, an effect we attribute to a decreased Thl immune response Hox alpha thus possibly presents us with a new therapeutic option fur prolonging remission in 1BD.