ABSTRACT
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.
Subject(s)
Animals , Mice , Cytokines , Dinoprostone , Glomerulonephritis, IGA , Immunoglobulin A , Interleukin-4 , Interleukin-5 , Ketotifen , Leukotriene B4 , Mast Cells , Membranes , Mice, Inbred ICR , Models, Animal , Models, Theoretical , Nitric Oxide , Th2 Cells , Transforming Growth Factor betaABSTRACT
Mesangial IgA nephropathy was experimentally induced in ddY mice by oral and parenteral administration of the poliomyelitis vaccine (POLIO), and we then tried to investigate if IgA deposition could be prevented by the concurrent use of sodium cromoglycate (SCG), which is known to inhibit the local mucosal immune reaction. Mucosal and systemic immunity could be induced by the administration of POLIO; proteinuria, increased serum IgA levels, mesangial cell proliferation, mesangial matrix widening, mesangial deposits of IgA, and large electron dense deposits in the mesangium were observed. Concurrent administration of SCG and POLIO resulted in a significant decrease in the serum IgA level and mesangial IgA deposits. The later addition or abstinence of SCG after the 70th day did not influence the glomerular mesangial IgA deposition. But the serum IgA level was still decreased by the continuous treatment of SCG even after the 70th day. Thus, mesangial IgA nephropathy simulating IgA nephropathy in humans could be induced in ddY mice using POLIO and its induction could largely be prevented by the concurrent use of SCG. However mesangial IgA deposits already present could not be cleared by the late administration of SCG.