Clinical Significance of Serum Th1-, Th2- and Regulatory T Cells-Associated Cytokines in Adult T-Cell Leukemia/Lymphoma: High Interleukin-5 and -10 Levels Are Significant Unfavorable Prognostic Factors.

Purpose & Experimental Design: Patients with adult T-cell leukemia/lymphoma (ATLL) are in a severely immunocompromised state, leading to frequent and severe infectious complications. Therefore, it is assumed that ATLL cells either express particular cytokines or induce their expression in host immune cells, disrupting the balanced production of cytokines and causing the host’s immune system to break down. We examined the levels of serum cytokines including T helper type 1- (Th1-)associated cytokines (IFN-γ, TNF-α, and IL-2), Th2-associated cytokines (IL-4, -5, and -6), and regulatory T cell-associated cytokines (IL-10 and TGF-β1) in 94 ATLL patients, 39 asymptomatic human T-cell lymphotropic virus type-1 (HTLV-1) carriers, and 50 healthy adult volunteers, in order to clarify whether elevated levels of particular cytokines are associated with the prognosis of ATLL patients.

Results: On multivariate analysis, high IL-5 and IL-10 levels were independent and significant unfavorable prognostic factors among the ATLL patients. The IL-10 level significantly increased with disease progression at each step from asymptomatic HTLV-1 carrier to ATLL of the indolent variant (chronic and smoldering subtypes) to ATLL of the aggressive variant (acute and lymphoma subtypes). Furthermore, high IL-10 was significantly associated with high LDH, indicating that the IL-10 level reflects the tumor burden. The IL-5 level was not associated with disease progression nor LDH. Among ATLL patients with the aggressive variant, high IL-5, but not high IL-10, was an independent and significant unfavorable prognostic factor on multivariate analysis.

Conclusions: The present study provide novel insights into the immunocompromised state of ATLL patients, and show that measurement of serum IL-5 and IL-10 levels is useful for predicting the prognosis and for determining a suitable treatment strategy for ATLL patients.