Effects of Ketotifen on an Experimental Model of IgA Nephropathy
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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-β , 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.
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-β , 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.
참고문헌 (31)
- Fox CC, "Enhancement of human intestinal mast cell mediator release in active ulcerative colitis", Gastroenterology, 99, pp.119~124 (1990)
- Konno S, "Inhibition of cytokine production from humanperipheral blood leukocytes by anti-allergic agents in vitro", Eur J Pharmacol, 264, pp.265~268
- Eliakim R, "Ketotifen effectively prevents mucosaldamage in experimental colitis", Gut, 33, pp.1498~1503 (1992)
- Karmeli F, "Gastric mucosal damage is mediated bysubstance P and prevented by ketotifen", Gastroenterology, 100, pp.1206~1216 (1991)
- Eliakim R, "Ketotifen-old drug, new indication: Reduction ofgastric mucosal injury", Scand J Gastroenterol, 28, pp.202~204 (1993)
- Sato M, "Relationship between serum IgA levels and CD4 subsets inIgA nephropathy", Nephron, 68, pp.20~24 (1994)
- Libetta C, "Circulating serum lectins of patients with IgA nephropathy stimulate IL-6 release from mesangial cells", J Am Soc Nephrol, 8, pp.208~213 (1997)
- Taniguchi Y, "Platelet-derived growth factor, IL-1 beta,IL-6R and tumor necrosis factor-alpha in IgA nephropathy. An immunohistochemicalstudy", Nephron, 74, pp.652~660 (1996)
- Parera M, "The role of IL2 and serum-soluble IL-2 receptorcells in idiopathic IgA nephropathy", Clin Immunol Immunopathol, 63, pp.196~199 (1992)
- Ashizawa M, "Detection of nuclear factor-kappa B in IgA nephropathy using Southwestern histochemistry", Am J Kidney Dis, 42, pp.76~86 (2003)
- Furusu A, "Involvement of IL4 in human glomerulonephritis: an in situ hybridization study of IL4 mRNA and IL-4 receptor mRNA", J Am Soc Nephrol, 8, pp.730~741 (1997)
- Montinaro V, "Extrarenal cytokines modulate the glomerular response to IgA immune complexes", Kidney Int, 42, pp.341~353 (1992)
- Chintalacharuvu SR, "The glycosylation of IgA produced by murine B cellsis altered by Th2 cytokines", J Immunol, 159, pp.2327~2333 (1997)
- Chintalacharuvu SR, "T cell cytokines determine the severity of experimental IgA nephropathy by regulating IgA glycosylation", Clin Exp Immunol, 126, pp.326~333 (2001)
- Narendranathan M, "Ketotifen in prevention of indomethacin-induced gastropathy", Indian J Gastoenterol, 18, pp.76~77 (1999)
- Jones NL, "Ketotifen therapy for acute ulcerative colitis in children: a pilot study", Dig Dis Sci, 43, pp.609~615 (1998)
- Sakamoto-Ihara T, "Possible involvement of mast cells in renal fibrosis in patients with IgA nephropathy", Inflamm Res, 56, pp.421~427 (2007)
- Ravinal RC, "Mast cells, TGF-beta1 and myofibroblasts expression in lupus nephritis outcome", Lupus, 14, pp.814~821 (2005)
- Heyman SN, "The effect of ketotifen on nitric oxidesynthase activity", Br J Pharmacol, 120, pp.1545~1551 (1997)
- Agmon Y, "Nitric oxide and prostanoids protectthe renal outer medulla from radiocontrast toxicity in the rat", J Clin Invest, 94, pp.1069~1075
- Kovcs T, "Do intestinal hyperpermeability and the related food antigens play a role in the progression of IgA nephropathy? I. Study of intestinal permeability", Am J Nephrol, 16, pp.500~505 (1996)
- Bazzi C, "Low dosesof drugs able to alter intestinal mucosal permeability to food antigens (5-aminosalicylic acid and sodium cromoglycate) do not reduce proteinuria in patientswith IgA nephropathy: a preliminary noncontrolled trial", Nephron, 61, pp.192~195 (1992)
- Sato M, "Effect of sodium cromoglycate on an experimentalmodel of IgA nephropahty", Clin Neph, 27, pp.141~146 (1987)
- Jin SY, "The effect of sodium cromoglycate on the induction of experimental IgA nephropathy", Yonsei Med J, 31, pp.33~48 (1990)
- Sato M, "Sodium cromoglycate therapy in IgA nephropathy: a preliminary short-term trial", Am J Kidney Dis, 15, pp.141~146 (1990)
- Yasuhiko T, "IgA nephropathy: lessons from an animal model, the ddY mouse", J Nephrol, 21, pp.463~467 (2008)
- Kivity S, "Effect of nedocromil sodium and cromolinesodium on atopic basophil function", Int J Immunopharmacol, 18, pp.75~78 (1996)
- Yan D, "Potential role for IL-5 and IL-6 in enhanced IgA secretion by Peyer's patch cells isolated from mice acutely exposed to vomitoxin", Toxicology, 122, pp.145~158 (1997)
- Xu-Amano J, "Helper T cell subsets for immunoglobulin A response: oralimmunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2cells in mucosa associated tissues", J Exp Med, 178, pp.1309~1320 (1993)
- H hara, "Drug induced cystitis due to ketotifen fumarate-a case report", Nippon Hinyokika GaKKai Zasshi, 83, pp.1906~1909 (1992)
- Cook HT, "Interleukin-4 ameliorates crescentic glomerulonephritis in Wistar Kyoto rats", Kidney Int, 55, pp.1319~1326 (1999)