Effect of IL-18 on leukocyte expression of iNOS and phospho-IkB in patients with squamous cell carcinoma of the oral cavity.

The inducible synthase of nitric oxide (iNOS) is responsible for the synthesis of nitric oxide (NO) in neutrophils (PMN) and in peripheral blood mononuclear cells (PBMC). This enzyme is controlled by a number of cytokines which accomplish their biological effect via e.g. activation of NF-kB pathway. The aim of the present study was to assess the expression of iNOS and production of NO by PMN and PBMC in patients with oral cavity squamous cell carcinoma (SCC), and to examine the role of the NF-kB pathway in the IL-18-stimulated activation of this enzyme. The production of NO and iNOS expression in PMN were reduced, while iNOS expression in PBMC was increased but NO production by these cells remain unchanged. Patients after treatment showed lower intensity of iNOS expression compared to that observed before treatment. Moreover, both before and after treatment iNOS expression was inversely correlated with phospho-IkB expression in PMN and in PBMC. Significantly higher levels of total NO were observed in the serum of Stage IV patients before and after treatment as compared to the control group. Altered expression of iNOS and NO generation by PMN and PBMC may have an unfavorable effect on the course of antineoplastic response in patients with squamous cell carcinoma of the oral cavity. Intensification of iNOS expression and NO production in Stage IV patients, induced by rhIL-18, suggests its beneficial effect on the activity of leukocytes in patients with squamous cell carcinoma of the oral cavity.