EFFECTS OF INTERLEUKIN-1-ALPHA, INTERLEUKIN-1 RECEPTOR ANTAGONIST, AND NEUTRALIZING ANTIBODY ON PROINFLAMMATORY CYTOKINE EXPRESSION BY HUMAN SQUAMOUS-CELL CARCINOMA LINES

Proinflammatory cytokines interleukin (IL)-1 alpha, IL-6, IL-8, and gr anulocyte macrophage colony-stimulating factor (GM-CSF) have been dete cted in tumor specimens and primary cell cultures from patients with h ead and neck squamous cell carcinoma. IL-1 alpha has been reported to play an important role in inducing the expression of cytokines IL-6, I L-8, and GM-CSF during inflammation. We examined whether these cytokin es are expressed together in Five primary and seven established UM-SCC cell lines, and we also examined the effects of IL-1 alpha, IL-1 rece ptor antagonist or neutralizing antibody (Ab) upon expression of this repertoire of proinflammatory cytokines in established UM-SCC lines. S ecretion of proinflammatory cytokines IL-1 alpha, IL-6, IL-8, and GM-C SF was detected by ELISA in both the primary and established UM-SCC li nes, Constitutive expression of specific mRNAs for these cytokines was confirmed in the UM-SCC lines by reverse transcriptase-PCR and Northe rn blot analysis, Addition of recombinant IE (rIL)-1 alpha but not rIL -6 induced a dose-dependent increase in IL-8 and GM-CSF production, IL -1 receptor antagonist (IL-RA) or anti-IL-1 neutralizing Ab could comp letely inhibit the rIL-1 alpha-inducible increase in IL-8 and GM-CSF e xpression, hut the inhibitors had a negligible effect on the constitut ive Level of production of the cytokines,Transfer and expression of th e IL-1 alpha gene in a low-cytokine-producing cell Line, UM-SCC-38, in duced IL-8 and GM-CSP expression, but this expression was also not inh ibited by IL-1RA or anti-IL-1 neutralizing Ab, We conclude that IL-1 a lpha can enhance the expression of cytokines IL-8 and GM-CSF in UM-SCC cell lines but that constitutive expression of these cytokines by UM- SCC is not inhibited by exogenous IL-1RA or neutralizing Ab.