Vitamin D derivatives: calcitriol and tacalcitol inhibits interleukin-6 and interleukin-8 expression in human nasal polyp fibroblast cultures.
OBJECTIVE
Biologically active vitamin D3 (VD) derivatives possess modulatory activities on immunological and inflammatory responses which can be reflected by altered levels of pro-inflammatory chemokines. Nasal polyposis (NP), defined as a chronic inflammatory process of upper respiratory system, could be influenced by VD derivatives. The purpose of this study was to investigate the influence of 1alpha,25-dihydroxyvitamin D3 (calcitriol) and 1alpha,24(R)-dihydroxyvitamin D3 (tacalcitol) on the secretion of IL-6 and IL-8 by fibroblasts derived from NP.


METHODS
The study involved 12 fibroblast cultures derived from NP samples obtained from surgically treated patients. Measurements were performed on the polyp cells after the 6-9 passages. Culture stimulation involved treatment with tacalcitol and calcitriol at a defined strength (from 10(-7)M to 10(-4)M). IL-6 and IL-8 concentrations were estimated with ELISA.


RESULTS
Treatment with calcitriol or tacalcitol inhibits the synthesis of both IL-6 and IL-8 compared to the control group. The dose dependence of this effect has been confirmed. VD derivatives influence was marked at higher concentrations. Significant interleukin decrease was observed at 10(-5) and 10(-4) for calcitriol and 10-4 in the case of tacalcitol.


CONCLUSIONS
The present study demonstrates that calcitriol and tacalcitol are capable of affecting pro-inflammatory cytokine (IL-6 and IL-8) levels in NP cultures. Our data imply a potential therapeutical application of topical VD derivates in NP and warrant further investigation.
Rostkowska-Nadolska
B
B
Department of Otolaryngology, Wroclaw Medical University, Wroclaw, Poland. beatanm@wp.pl
Sliupkas-Dyrda
E
E
Potyka
J
J
Kusmierz
D
D
Fraczek
M
M
Krecicki
T
T
Kubik
P
P
Zatonski
M
M
Latocha
M
M
D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D009298:Nasal Polyps / Q000473:pathology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology*
D004100:Dihydroxycholecalciferols; D015850:Interleukin-6; D016209:Interleukin-8; D014807:Vitamin D; C023850:1 alpha,24-dihydroxyvitamin D3; D002117:Calcitriol