Improved pruritus correlates with lower levels of IL-31 in CTCL patients under different therapeutic modalities

- Corticosteroids and histone deacetylase inhibitors decrease expression of IL-31.
- Treated Sezary patients show lower levels of IL-31 coinciding with less pruritus.
- IL-31-producing malignant T cells express the chemokine receptor type-4 (CCR4).

Pruritus is one of the cardinal symptoms found in patients with leukemic cutaneous T cell lymphoma (CTCL). The nature of the pruritus experienced by CTCL patients is complex, involving different pathways and cell mediators, thus making it poorly responsive to conventional anti-itch therapies. Recent reports highlight the role of interleukin 31 (IL-31) as a novel cytokine involved in the pathogenesis of pruritus in atopic dermatitis and CTCL. Here we provide both in vivo and in vitro evidence suggesting that histone deacetylase (HDAC) inhibitors may mitigate itch through lowering of levels of IL-31-expressing T cells. Furthermore, we demonstrate that chemokine receptor type-4 (CCR4)-bearing T cells are a main source of IL-31 in CTCL, and that neutralizing the IL-31 pathway through targeting of the CCR4-expressing T cells may represent a promising therapeutic strategy for symptomatic relief in CTCL.