Interleukin-16 as a Marker of Sezary Syndrome Onset and Stage

S,zary 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. 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. 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 S,zary syndrome, indicating this loss is not reversible. We propose that it is feasible to use plasma levels of IL-16 as a potential diagnostic marker of S,zary syndrome and to use loss of intracellular IL-16 as a prognostic indicator of disease severity and stage.