Th2 cytokine mRNA expression in primary cutaneous CD30-positive lymphoproliferative disorders: successful treatment with recombinant interferon-gamma.
Primary cutaneous CD30 (Ki-1)+ large cell lymphoma (KiL) and lymphomatoid papulosis (LyP) type A are collectively termed as primary cutaneous CD30-positive lymphoproliferative disorders. We examined the cytokine profile of skin-infiltrating cells and the therapeutic efficacy of recombinant interferon-gamma (rIFN-gamma) in primary cutaneous KiL and LyP type A. By reverse transcriptase-polymerase chain reaction, mRNAs for interleukin-4 (IL-4) and IL-10 were detected in the dermis of skin lesions in all cases (three cases of KiL and four cases of LyP). In addition, tissue from one KiL patient transcribed IL-2 and IFN-gamma messages, and one LyP patient showed IL-2 mRNA. In contrast, normal skin from ten healthy donors contained mRNA for IL-2 or IFN-gamma, or both, but not for IL-4. Before the therapeutic trial of rIFN-gamma, the response of skin lesions was assessed by a predictive skin test with local injection of rIFN-gamma (0.5 x 10(6) Japan Reference Units [JRU; 1 JRU roughly corresponds to 4 NIH units]) for 3 consecutive days in two KiL and two LyP patients. Numbers of skin-infiltrating CD30+ cells were decreased, and transcription of mRNA for IL-4 and IL-10 was downregulated after the skin test in one KiL and two LyP cases. One KiL patient showed no histologic response or change in mRNA expression. In the therapeutic trial, rIFN-gamma (total doses of 1.2-4.0 x 10(7) JRU) was administered intravenously (n = 2) or locally (n = 2). In three patients who responded to the skin test, the lesions were objectively improved and the numbers of skin-infiltrating CD30+ cells were markedly decreased after the therapeutic trial. No improvement was observed in one KiL patient who did not respond to the skin test. These findings suggest that the skin-infiltrating CD30+ cells in KiL and LyP have a Th2 cytokine profile and raise the possibility that the administration of rIFN-gamma improves the conditions by inhibiting cytokine mRNA transcription and proliferation of CD30+ cells.
Yagi
H
H
Department of Dermatology, Hamamatsu University School of Medicine, Japan.
Tokura
Y
Y
Furukawa
F
F
Takigawa
M
M
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D017252:CD3 Complex / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000627:therapeutic use*; D007378:Interleukins / Q000032:analysis / Q000235:genetics; D017730:Ki-1 Antigen / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D017731:Lymphomatoid Papulosis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D012867:Skin / Q000473:pathology; D016176:T-Lymphocyte Subsets
D000970:Antineoplastic Agents; D017252:CD3 Complex; D007378:Interleukins; D017730:Ki-1 Antigen; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma