IL-31 and IL-8 in Cutaneous T-Cell Lymphoma: Looking for Their Role in Itch

Abstract

The itch associated with cutaneous T-cell lymphoma (CTCL), including Mycosis Fungoides (MF) and Sézary syndrome (SS), is often severe and poorly responsive to treatment with antihistamines. Recent studies have highlighted the possible role of interleukins in nonhistaminergic itch. We investigated the role of IL-31 and IL-8 in CTCL, concerning disease severity and associated itch. Serum samples of 27 patients with CTCL (17 MF and 10 SS) and 29 controls (blood donors) were analyzed for interleukin- (IL-) 31 and IL-8; correlations with disease and itch severity were evaluated. IL-31 serum levels were higher in CTCL patients than in controls and higher in SS than in MF. Also, serum IL-31 levels were higher in patients with advanced disease compared to those with early disease, and they correlated positively with lactate dehydrogenase and beta 2-microglobulin levels, as well as with the Sézary cell count. Itch affected 67% of CTCL patients (MF: 47%; SS: 100%). Serum IL-31 levels were higher in itching patients than in controls and in patients without itching. There was no association between serum IL-8 and disease severity, nor with itching. Serum IL-8 levels correlated positively with peripheral blood leukocyte and neutrophil counts in CTCL patients. Our study suggests a role for IL-31 in CTCL-associated itch, especially in advanced disease and SS, offering a rational target for new therapeutic approaches. Increased serum IL-8 observed in some patients may be related to concomitant infections, and its role in exacerbating itch by recruiting neutrophils and promoting the release of neutrophil proteases deserves further investigation.

IL-31: State of the Art for an Inflammation-Oriented Interleukin

“…Overall, results indicate that IL-31 levels relate to itch severity but not necessarily to disease stage [ 85 ]. Perhaps, different stages of the same pathological entities could explain the different results [ 86 ].…”

CD30+ Transformed Mycosis Fungoides Associated with Sweet-like Dermatosis

“…In human skin, an exclusive infiltration of neutrophils due to IL-8 production has been shown. IL-8 can also be synthetized by neutrophils, which may thus intensify their own recruitment ( 13 ).…”

Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma

“…IL-31 has been widely implied in CTCL-associated pruritus in patients (61)(62)(63). To investigate the role of IL-31 signaling in CTCL-induced itch in mice, we conducted in situ hybridization, ELISA, and behavioral analyses.…”