The malignant cells in Sezary syndrome express the skin trafficking molecules' cutaneous lymphocyte associated antigen (CLA) and chemokine receptor 4 (CCR4). High levels of the CCR4 ligand, thymus, and activation-regulated chemokine (TARC), have been reported in the blood and skin of patients. The rexinoid X-receptor specific retinoid, bexarotene, has contributed to the resolution of cutaneous disease among patients. To evaluate the effects of bexarotene on skin trafficking molecule expression and chemotaxis, peripheral blood mononuclear cells from Sezary syndrome patients and healthy controls were treated with bexarotene in vitro. CCR4 and CLA expression levels and chemotaxis in response to TARC (6.25 ng/ml) were evaluated among lymphocytes before and after treament with bexarotene (10 lM). Flow cytometric analysis was performed to evaluate CD4, CD26, CLA, and CCR4 cell surface expression. Transwell migration assays were performed to evaluate chemotaxis to TARC. Prior to treatment, malignant cells exhibited higher CCR4 expression (45-90%) and greater than four times more chemotaxis to TARC compared with healthy controls. After treatment with bexarotene for 36-96 hr, a 28% reduction in CCR4 expression was noted (P < 0.05) among the malignant population with an associated 9% decrease in chemotaxis to TARC (P < 0.05). Our results show that bexarotene may inhibit malignant cell trafficking to the skin through an ability to suppress CCR4 expression among Sezary syndrome lymphocytes. Am. J. Hematol. 82:792-797, 2007. V
A 2-year-old female spayed domestic shorthair cat was examined because of lethargy, inappetance, vocalization, and abnormal aggressive behavior of 1 day's duration. The cat had been groomed the previous day with a d-limonene-based insecticidal shampoo. Skin lesions consisted of coalescing erythematous patches. Despite supportive care, the cat's condition deteriorated. Dermatohistopathologic changes included multifocal areas of acute coagulative epidermal necrosis. The dermis was infiltrated by a dense population of bacilli. d-Limonene toxicosis has been rarely described in dogs and cats. Toxic effects such as hypersalivation, ataxia, shivering, hypothermia, scrotal irritation, hypotension, and erythema multiforme major have been reported. Treatment for septicemia and disseminated intravascular coagulation, along with intensive supportive care, may be necessary.
It has long been known that certain immune augmenting therapeutics, particularly interferon alpha, can exert profound salutary effects on the clinical progress of patients with cutaneous T-cell lymphoma. Emerging evidence that the host immune response may play an important role in the control of this disorder has led to the clinical application of other cytokines including interleukin-12 and interferon gamma. In this review, the authors will summarize current knowledge regarding the use of cytokines, fusion proteins and antibodies for the treatment of cutaneous T-cell lymphoma.
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