Interleukin-16 as a marker of Sézary syndrome onset and stage

Introduction: Sézary syndrome is one of the most common forms of cutaneous T cell lymphoma (CTCL). It is characterized by skin infiltration of malignant T cells. We examined interleukin-16, a potent T cell chemoattractant and cell-cycle regulator, as a prospective marker of disease onset and stage. Methods: The correlation of total intracellular interleukin-16 and surface CD26 was studied by flow cytometry. Confocal microscopy was performed to determine localization of interleukin-16 at different stages of the disease. The levels of interleukin-16 in plasma and culture supernatants were examined by enzyme-linked immunoassay. Additionally, lymphocytes from stage IB patients were cultured in the presence of interleukin-16 alone and in combination with interleukin-15, and their ability to survive and proliferate was determined by cell counts and [3H]TdR incorporation. Results: The data indicate that loss of both nuclear and intracellular pro-interleukin-16 highly correspond to disease stage, with a concomitant increase in secreted mature interleukin-16 in both culture supernatants and patients' plasma that peaks at stage IB. Loss of intracellular interleukin-16 strongly corresponded to loss of surface CD26, which has been shown to occur with more advanced stage of CTCL. Nuclear translocation of pro-interleukin-16 was not observed in late stages of Sézary syndrome, indicating this loss is not reversible. Conclusions: We propose that it is feasible to use plasma levels of IL-16 as a potential diagnostic marker of Sézary syndrome and to use loss of intracellular IL-16 as a prognostic indicator of disease severity and stage.