Interleukin-1 receptor antagonist in head and neck squamous cell carcinoma

Abstract

Background: We hypothesized that in head and neck squamous cell carcinoma, the overexpression of protumorigenic interleukin-1 (IL-1) activity within the tumor tissue is a result of decreased expression of the specific antagonist or inhibitor (ie, IL-1 receptor antagonist) by the tumor cells. Ultimately, this local overexpression of IL-1 activity increases tumor growth and metastasis.

Design: To test our hypotheses, immunologic analysis for IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist was performed on histologic sections and tumor homogenates of human head and neck squamous cell carcinomas.

Setting: University teaching hospital.

Patients or other participants: Normal and tumor specimens were obtained from patients undergoing surgical resections of the head and neck for benign and malignant disease.

Results: Immunohistochemical analysis demonstrated the presence of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist within tumor cells and inflammatory cells in the tumor stroma in 19 of 19 tumor specimens. Quantitatively, IL-1 alpha was present in 19 of 19 tumor specimens (1.97 +/- 0.46 ng/mg of total protein [mean +/- SD]) and 5 of 9 normal specimens (0.23 +/- 0.12 ng/mg of total protein). All specimens contained IL-1 beta in detectable quantities (1.60 +/- 0.29 ng/mg of total protein in tumor specimens and 0.189 +/- 0.04 ng/mg of total protein in normal specimens). All specimens contained IL-1 receptor antagonist (368.87 +/- 57.63 ng/mg of total protein in tumor specimens and 585.10 +/- 166.03 ng/mg of total protein in normal specimens). The mean total IL-1/IL-1 receptor antagonist ratio was 13.26 +/- 2.31 in patients with cancer compared with 0.997 +/- 0.26 in normal patients.

Conclusions: The increased IL-1 index in the cancer state compared with the normal state reflects an imbalance of IL-1 and IL-1 receptor antagonist, which may contribute to unrestricted growth and metastasis of head and neck squamous cell carcinoma.