INTERLEUKIN-10 AS A POSSIBLE MEDIATOR OF IMMUNOSUPPRESSIVE EFFECT IN PATIENTS WITH SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK

Background: Depressed cell-mediated immunity is a frequent event in pa tients with head and neck cancer and is characterized by impairment of T cell-proliferative responses and natural killer cell and lymphokine -activated killer cell activity, This immunosuppressive effect appears to be mediated by a serum-derived factor, Certain cytokines, includin g transforming growth factor-beta (TGF-beta) and interleukin (IL)-10 h ave been shown to induce similar immunosuppressive effects. The presen t study was designed to examine the putative role of these cytokines i n cellular immune suppression induced by patient serum. Methods: Serum was collected from multiple patients with newly diagnosed or recurren t squamous cell carcinoma of the head and neck, The serum was heat ina ctivated for 30 min and frozen in aliquots. Peripheral blood lymphocyt es were isolated from normal human blood, Lymphocytes were suspended i n RPMI and 15% concentrations of control and patient serum and stimula ted with 0.75 mg% phytohemagglutinin. Tn addition, neutralizing antibo dies to TGF-beta and IL-10 were added to lymphocyte cultures, At 24 h, an IL-2 response assay was performed. Finally, the sera were examined for the presence of TGF-beta and IL-10 using an enzyme-linked immunos orbent assay (ELISA). Results: In seven of seven experiments, incubati ng cells with a neutralizing antibody to TGF-beta failed to counteract the immune suppression and restore proliferative response to IL-2, Al so, an ELISA of these sera failed to demonstrate the presence of TGF-b eta, In contrast, four of five experiments performed with neutralizing antibody to IL-10 showed significant restoration of proliferation in the presence of this antibody, Also, ELISA showed elevated IL-10 level s in 65% of the patients' sera in comparison to controls. Conclusion: We conclude that TGF-beta is not responsible for the immunosuppressive effects induced by head and neck patient sera, However, the suppressi ve effect is reversed by blocking the biologic action of IL-10, Furthe r experiments are needed to define the role of IL-10 in inducing the i mmunosuppressive effect.