PURPOSE: The intestinal mucosal defect has been known as one of the pathogenicmechanisms of IgA nephropathy. Oral antigens usually induce the activation of Th2 cells and mast cells. These cells secrete cytokines IL-4, IL-5 and TGF-beta, which increase IgA production. Although ketotifen (benzocycloheptathiophene) is an H1 antagonist and a mast cell membrane stabilizer, it could protect the gastrointestinal membrane through inhibiting the production of IL-4, IL-5, PGE2, and LTB4, and decreasing the activity of nitric oxide synthease. Therefore, we have investigated if ketotifen may protect the development of IgA nephropathy with an oral antigen. METHODS: ICR mice were used as an animal model orally with Poliovax only [ketotifen (-)], the other group was given oral ketotifen [ketotifen (+)] in addition to Poliovax. RESULTS: Mesangial IgA deposition developed in 11 out of the 18 mice in the ketotifen (-) group, while in three out of the nine mice in ketotifen (+) group. The mesangial change developed in 16 out of the 18 mice in the ketotifen (-) group, while in five out of the nine mice in the ketotifen (+) group. Serum IL-4 and IL-5 levels were not significantly lower in the latter group than in the former. CONCLUSION: According to the statistical results from the above, ketotifen therapy would be beneficial to reducing mesangial changes in IgA nephropathy.
Animals ; Cytokines ; Dinoprostone ; Glomerulonephritis, IGA ; Immunoglobulin A ; Interleukin-4 ; Interleukin-5 ; Ketotifen ; Leukotriene B4 ; Mast Cells ; Membranes ; Mice ; Mice, Inbred ICR ; Models, Animal ; Models, Theoretical ; Nitric Oxide ; Th2 Cells ; Transforming Growth Factor beta