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 (Kit) 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 Kit 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 Kit 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 Kit and two LyP cases. One Kit 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 Kit patient who did not respond to the skin test, These findings suggest that the skin-infiltrating CD30(+) cells in Kit 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.