Oral treatment with a vitamin D3 analogue (BXL628) has anti-inflammatory effects in rodent model of interstitial cystitis.
OBJECTIVE
To investigate the effects of a vitamin D3 analogue (BXL628) in a model of chronic cystitis, as calcitriol analogues might be an interesting new therapeutic option for interstitial cystitis, for although the cause of the disease remains unclear, the increase in mast cells in the mucosa and detrusor muscle are significant.


METHODS
We devised a mouse model of allergen-induced allergic cystitis that is associated with the up-regulation of genes for interleukin-13, FcepsilonRIalpha and mast cells-derived proteases, a massive inflammatory reaction in the bladder tissue, and augmented levels of mast cell-derived protease 1 (MMCP1) detected in mouse sera.


RESULTS
Oral administration of BXL628 significantly reduced the expression of interleukin-13, FcepsilonRIalpha and MMCP1 in the bladder. Furthermore, histological analysis showed a decrease in oedema and leukocyte infiltration in the bladder wall. BXL628 treatment reduced serum MMCP1 levels, indicating an effect on mast cell degranulation in vivo.


CONCLUSIONS
Vitamin D3 analogues may successfully be used as anti-inflammatory agents in allergen-mediated inflammatory reactions. Moreover, the modulatory effect shown on mast cell activation by the BXL628 analogue strongly supports its potential therapeutic use in a possibly mast cell-dependent disease such as human interstitial cystitis.
Benigni
Fabio
F
BioXell SpA, Milano, Italy. fabio.benigni@bioxell.com
Baroni
Enrico
E
Zecevic
Marija
M
Zvara
Peter
P
Streng
Tomi
T
Hedlund
Petter
P
Colli
Enrico
E
D'Ambrosio
Daniele
D
Andersson
Karl-Erik
KE
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002762:Cholecalciferol / Q000031:analogs & derivatives; D018856:Cystitis, Interstitial / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C
D000893:Anti-Inflammatory Agents; C487049:BXL628; D018793:Interleukin-13; D002762:Cholecalciferol; D002117:Calcitriol