NF-κB dependent cytokine levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma

Previous investigations in our laboratory and others (Chen et al., 1998) have shown that the levels of certain inflammatory, proangiogenic cytokines in saliva and tissue specimens of patients with oral premalignant lesions (OPML) are elevated. We have also shown that these cytokines are elevated in tissue culture of oral squamous cell carcinoma (OSCC) cell lines. The purpose of this pilot study was to determine the level of several inflammatory, NF-κB-dependent cytokines in whole unstimulated saliva (WUS), in subjects with OPML as compared to those with diagnosed OSCC. Subjects (n = 13) with OMPL, OSCC (n = 13), and age-sex matched controls without oral lesions (C) (n = 13) were enrolled. The mean age was 58.7 years. WUS was collected by standard techniques for 5 min (Navazesh, 1993). WUS samples were centrifuged and the cytokine analysis was performed on the supernatants by ELISA as previously described by Ondrey et al. (1991). The cytokines analyzed were: TNF-alpha, interleukin-1, interleukin-6, and interleukin-8 (TNF-α, IL-1, IL-6, and IL-8). The results as analyzed by Pairwise t-tests revealed significant differences in the salivary levels of: (1) TNF-α: (mean ± S.E.M.: TNF-α-OSSC = 28.9 ± 14.6* pcg/ml versus OPML = 10.5 ± 7.4* pcg/ml versus controls = 3.0 ± 1.0 pcg/ml; *p < 0.01); (2) IL-1: (IL-1-OSSC = 454.4 ± 215.8* pcg/ml versus OPML = 255.1 ± 124.8* pcg/ml versus controls = 173.2 ± 66.9 pcg/ml; *p < 0.01); (3) IL-6: (mean ± S.E.M.: IL-6-OSSC = 88.2 ± 43.2* pcg/ml versus OPML = 70.8 ± 24.3* pcg/ml versus controls = 1.4 ± 1.0 pcg/ml; *p < 0.001) and (4) IL-8 in saliva: (mean ± S.E.M.: IL-8-OSSC = 3154.1 ± 1023.2* pcg/ml versus OPML = 1918.2 ± 899.1* pcg/ml versus controls = 1580.7 ± 789.0 pcg/ml; *p < 0.001). There was a significant increase in the levels of all cytokines in the saliva of the OPML as compared to controls, and a significant difference in the cytokines of OSSC saliva compared to the OPML and controls. These results suggest that these proangiogenic, proinflammatory cytokines are elevated in the saliva of patients with OSSC and OPML as compared to controls, which may have diagnostic and/or prognostic significance.