Salivary levels of NF-kappa B dependent cytokines of patients with oral squamous cell carcinoma

N.L. Rhodus, DMD, MPH, VU Ho,MD, C. S. Miller, DMD, MS, J. Burt,DMD, F. Ondrey, MD, PhD

University of Minnesota, Minneapolis, MN.

Previous investigations in our laboratory and others (Yamamoto,,1994) 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 also elevated in tissue culture of oral squamous cell carcinoma (OSCC) cell lines. AIM : The purpose of this pilot study was to determine the level of several inflammatory, NF-kappa B dependent cytokines in whole unstimulated saliva (WUS), in subjects with OPML as compared to those with diagnosed OSCC . METHODS: A group of subjects ( n= 13) with OMPL and a group with definitively diagnosed OSCC ( n= 13) were enrolled in the study as were age-sex matched controls without oral lesions (C)(n= 13). The mean age was 58.7 yrs. WUS was collected by standard techniques for 5 min.(Navazesh, 1993) . The cytokines analyzed were: TNF-alpha, IL-1, IL-6, IL-8. Samples were centrifuged and the cytokine analysis was performed on the supernatants by ELISA as previously described by Ondrey, ( 1991). RESULTS: The results as analyzed by Pairwise t-tests revealed significant differences in the salivary levels of : 1.) TNF- alpha : ( mean ± SEM: TNF- alpha-OPML = 10.5 ± 11.6* vs. OSSC= 28.9 ± 14.6* vs. controls = 3.0± 1.0 ug/ml; *p < 0.01); 2.) IL-1 : ( IL-1-OPML = 255.1 ± 137.2* vs. OSSC= 454.4 ± 215.8* vs. controls =173.2 ± 66.9 ug/ml ; *p < 0.01 ), 3.) IL-6 in saliva :( mean ± SEM: IL-6-OPML = 70.8 ± 24.3* vs. OSSC= 88.2 ± 43.2* vs. controls = 1.4± 1.0 ug/ml; *p < 0.001). and, 4.) IL-8 in saliva : ( mean ± SEM: IL-8 -OPML = 1918.2 ± 899.1* vs. OSSC= 3154.1 ± 1023.2* vs. controls = 1580.7 ± 789.0 ug/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 . CONCLUSIONS: These preliminary results indicate that inflammatory cytokines may be elevated in the saliva of patients with OSSC and OPML as compared to controls, which may have diagnostic and/or prognostic significance .

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prognostic Markers.