SERUM LEVELS OF CYTOKINES IN PATIENTS WITH UNTREATED PRIMARY LUNG-CANCER

To evaluate the relationships between serum endogenous cytokine levels and their clinical implications in cancer patients, we measured the s erum levels of endogenous granulocyte colony-stimulating factor (G-CSF ), granulocyte-macrophage colony-stimulating factor (GM-CSF), macropha ge colony-stimulating factor (M-CSF), and interleukin 6 (IL-6) in pati ents with untreated primary lung cancer. The serum G-CSF level was mea sured using a chemiluminescent ELISA, and the other cytokine levels we re measured using ELISA. Fifty healthy adults and 183 patients with pr imary lung cancer were studied. The mean M-CSF level in the lung cance r patients (1106.4 units/ml) was significantly higher than that in the healthy adults (836 units/ml, P = 0.0001). In patients with large cel l carcinoma, endogenous G-CSF, M-CSF, and IL-6 levels were significant ly higher than those in patients with carcinomas of other cell types ( P < 0.05). Univariate analysis showed that survival of 159 non-small c ell lung cancer patients with high (more than cutoff level) G-CSF, M-C SF, and IL-6 levels was significantly poorer than that of patients wit h low levels (Wilcoxon's test, P = 0.018, P < 0.0001, and P < 0.0001, respectively). Survival of patients with high levels of two or more cy tokines was poorer than that of those with high levels of one cytokine or normal cytokine levels (P < 0.0001). Multivariate analysis using C ox's proportional hazards model showed that high M-CSF and C-reactive protein levels correlated significantly with poor survival (P = 0.037 and 0.037, respectively). Our preliminary data suggest that high M-CSF levels in nonsmall cell lung cancer may he of poor prognostic value.