Topical calcitriol (1,25-dihydroxyvitamin D3) treatment of psoriasis: an immunohistological evaluation.
The potent calciotropic hormone calcitriol (1,25-dihydroxyvitamin D3, 1,25(OH)2D3) has been shown to be very effective and safe in the topical treatment of psoriasis. In vitro, 1,25(OH)2D3 inhibits proliferation and stimulates differentiation of human keratinocytes. Increasing evidence suggests an immunoregulatory function of this potent steroid hormone. To further characterize the biological effects of topical calcitriol treatment in psoriasis, we have analyzed immunohistochemically the expression of markers for epidermal proliferation (proliferating cell nuclear antigen=PCNA) and differentiation (transglutaminase K, involucrin, cytokeratin 16), as well as inflammation (CD1a, 55 kDa TNF-receptor, NAP-1/IL-8) in calcitriol-treated psoriatic skin in situ. Our findings strongly support the hypothesis that calcitriol modulates keratinocyte proliferation/differentiation as well as inflammation in human skin in vivo. The immunoreactivity of markers for epidermal proliferation and differentiation, as well as of CD1a and NAP-1/IL-8, changed after 8 weeks of calcitriol treatment almost completely to the pattern characteristic for non-lesional psoriatic skin, while a large number of 55 kDa TNF-receptor positive cells could be found in the dermal compartment.
Reichrath
J
J
Vitamin D, Skin, and Bone Research Laboratory, Endocrinology Department of Medicine, Boston University Medical Center, MA 02118, USA.
Perez
A
A
Müller
S M
SM
Chen
T C
TC
Kerber
A
A
Bahmer
F A
FA
Holick
M F
MF
D000287:Administration, Topical; D018949:Antigens, CD1 / Q000032:analysis; D002117:Calcitriol / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000032:analysis; D015603:Keratinocytes / Q000473:pathology; D007633:Keratins / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D012867:Skin / Q000737:chemistry / Q000473:pathology; D011503:Transglutaminases / Q000032:analysis
D018949:Antigens, CD1; D016209:Interleukin-8; D018809:Proliferating Cell Nuclear Antigen; D011498:Protein Precursors; D018124:Receptors, Tumor Necrosis Factor; C032253:involucrin; D007633:Keratins; D011503:Transglutaminases; C105804:transglutaminase 1; D002117:Calcitriol