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 patients 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, including transforming growth factor-beta (TGF-beta) and interleukin (IL)-10 have been shown to induce similar immunosuppressive effects. The present study was designed to examine the putative role of these cytokines in cellular immune suppression induced by patient serum.


METHODS
Serum was collected from multiple patients with newly diagnosed or recurrent squamous cell carcinoma of the head and neck. The serum was heat inactivated for 30 min and frozen in aliquots. Peripheral blood lymphocytes were isolated from normal human blood. Lymphocytes were suspended in RPMI and 15% concentrations of control and patient serum and stimulated with 0.75 mg% phytohemagglutinin. In addition, neutralizing antibodies to TGF-beta and IL-10 were added to lymphocyte cultures. At 24 h, and IL-2 response assay was performed. Finally, the sera were examined for the presence of TGF-beta and IL-10 using an enzyme-linked immunosorbent assay (ELISA).


RESULTS
In seven of seven experiments, incubating cells with a neutralizing antibody to TGF-beta failed to counteract the immune suppression and restore proliferative response to IL-2. Also, an ELISA of these sera failed to demonstrate the presence of TGF-beta. 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 levels in 65% of the patients' sera in comparison to controls.


CONCLUSIONS
We conclude that TGF-beta is not responsible for the immunosuppressive effects induced by head and neck patient sera. However, the suppressive effect is reversed by blocking the biologic action of IL-10. Further experiments are needed to define the role of IL-10 in inducing the immunosuppressive effect.
Avradopoulos
K
K
Roger Williams Medical Center, Brown University, Providence, Rhode Island 12908-4735, USA.
Mehta
S
S
Blackinton
D
D
Wanebo
H J
HJ
D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10