J Korean Soc Pediatr Nephrol.  2009 Oct;13(2):153-160.

Effects of Ketotifen on an Experimental Model of IgA Nephropathy

• Do YS
• Soon EJ
• Namgoong M

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.

Keyword

Experimental IgA Nephropathy; IL-4; IL-5; Benzocycloheptathiophene (Ketotifen)

MeSH Terms

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
Cytokines
Dinoprostone
Immunoglobulin A
Interleukin-4
Interleukin-5
Ketotifen
Leukotriene B4
Nitric Oxide
Transforming Growth Factor beta