Cytokine mRNA levels in Alopecia areata before and after treatment with the contact allergen diphenylcyclopropenone.
Although the nature of the noxious signal and the anatomical target in alopecia areata (AA) are still unknown, it has been assumed that CD4+ T lymphocytes surrounding and infiltrating the hair bulb might trigger the hair loss. As these T lymphocytes do not promote cytotoxic activity we hypothesize that AA is triggered by cytokines. Topical immunotherapy with diphenylcyclopropenone (DCP) is at present the most effective approach. If it is true that AA results from a distinct cytokine pattern, we can hypothesize that the beneficial effect of DCP should be mediated by locally secreted cytokines during the contact allergy. Using semiquantitative reverse transcription-polymerase chain reaction with RNA extracted from scalp biopsies from patients with AA before and after successful treatment with DCP, and from healthy controls we detected a T-cell response with increased steady state mRNA levels for interferon (IFN)-gamma, interleukin (IL)-1 beta, and IL-2 in untreated AA of the totalis type. After DCP treatment, the IFN-gamma expression was reduced but still above the constitutive level found in controls, whereas mRNA expression of IL-2, IL-8, IL-10, and tumor necrosis factor-alpha was increased. Our results point towards cytokines involved in the pathogenesis in AA. A TH1 type cytokine pattern is present in untreated AA, and this is modified by cytokines secreted during DCP treatment. IL-10 has recently been described as an immunomodulator of the TH1 response and, therefore, we hypothesize that basal keratinocytes or lesional T cells secrete bioactive IL-10 after DCP application, resulting in an inhibitory effect on lesional T lymphocytes. This hypothesis would explain the effectiveness of DCP and implies the theoretical possibility of a response to topical or intralesional application of recombinant IL-10.
Hoffmann
R
R
Department of Dermatology, Philipp University, Marburg, Germany.
Wenzel
E
E
Huth
A
A
van der Steen
P
P
Schäufele
M
M
Henninger
H P
HP
Happle
R
R
D000328:Adult; D000368:Aged; D000485:Allergens / Q000494:pharmacology; D000506:Alopecia Areata / Q000235:genetics*; D001706:Biopsy; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003521:Cyclopropanes / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics*; D003877:Dermatitis, Contact / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis*; D012535:Scalp / Q000473:pathology
D000485:Allergens; D003521:Cyclopropanes; D016207:Cytokines; D012333:RNA, Messenger; C029402:diphenylcyclopropenone