INTERLEUKIN-1 RECEPTOR ANTAGONIST IN HEAD AND NECK SQUAMOUS-CELL CARCINOMA

Background: We hypothesized that in head and neck squamous cell carcin oma, the overexpression of protumorigenic interleukin-1 (IL-1) activit y within the tumor tissue is a result of decreased expression of the s pecific antagonist or inhibitor (ie, IL-1 receptor antagonist) by the tumor cells. Ultimately, this local overexpression of IL-1 activity in creases tumor growth and metastasis. Design: To test our hypotheses, i mmunologic analysis for IL-1 alpha, IL-1 beta, and IL-1 receptor antag onist was performed on histologic sections and tumor homogenates of hu man head and neck squamous cell carcinomas. Setting: University teachi ng hospital. Patients or Other Participants: Normal and tumor specimen s were obtained from patients undergoing surgical resections of the he ad and neck for benign and malignant disease. Results: Immunohistochem ical 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 alp ha 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 o f total protein). All specimens contained IL-1 beta in detectable quan tities (1.60+/-0.29 ng/mg of total protein in tumor specimens and 0.18 9+/-0.04 ng/mg of total protein in normal specimens). All specimens co ntained IL-1 receptor antagonist (368.87+/-57.63 ng/mg of total protei n in tumor specimens and 585.10+/-166.03 ng/mg of total protein in nor mal 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 no rmal patients. Conclusions: The increased IL-1 index in the cancer sta te compared with the normal state reflects an imbalance of IL-1 and IL -1 receptor antagonist, which may contribute to unrestricted growth an d metastasis of head and neck squamous cell carcinoma.