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Interleukin-10 as a possible mediator of immunosuppressive effect in patients with squamous cell carcinoma of the head and neck

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Abstract

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-β) 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-β 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-β and IL-10 using an enzyme-linked immunosorbent assay (ELISA).

Results: In seven of seven experiments, incubating cells with a neutralizing antibody to TGF-β 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-β. 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.

Conclusion: We conclude that TGF-β 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.

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, Roger Williams Medical Center, Brown University, 877 Chalkstone Avenue, 12908-4735, Providence, RI, USA

    Konstantine Avradopoulos MD, S. Mehta PhD, D. Blackinton MD &  Harold J. Wanebo MD

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  1. Konstantine Avradopoulos MD
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  2. S. Mehta PhD
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  3. D. Blackinton MD
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  4. Harold J. Wanebo MD
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Avradopoulos, K., Mehta, S., Blackinton, D. et al. Interleukin-10 as a possible mediator of immunosuppressive effect in patients with squamous cell carcinoma of the head and neck. Annals of Surgical Oncology 4, 184–190 (1997). https://doi.org/10.1007/BF02303803

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  • DOI: https://doi.org/10.1007/BF02303803

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