INTERLEUKIN-1-ALPHA AND INTERLEUKIN-6 PROMOTE THE IN-VITRO GROWTH OF BOTH NORMAL AND NEOPLASTIC HUMAN CERVICAL EPITHELIAL-CELLS

Interleukin 1 alpha (IL-1 alpha), Interleukin 6 (IL-6) and epidermal g rowth factor (EGF) were tested for their ability to regulate epithelia l cervical cell cytokine production and secretion and to induce prolif eration of human normal and neoplastic epithelial cervical cells. IL-1 alpha, and IL-6 enhanced tumour and normal cell growth by 20-120%. Th e interleukins efficacy was similar to that of EGF for some cell lines but not for normal esocervical cells. The stimulatory effects of the interleukins were observed in both human papilloma virus (HPV)-infecte d and HPV-non-infected cervical cells. Normal cells constitutively exp ressed IL-1 alpha, IL-6 and EGF mRNA. All cell lines except C33A expre ssed IL-1 alpha mRNA. CaSki, C-411 and HT-3 expressed mRNA for IL-6. I L-1 alpha induced or increased IL-6 mRNA levels in the Me-180 and HT-3 lines and in normal cervical cells. IL-6 induced: (1) the expression of its own mRNA only in Me-180 cells that constitutively lacked IL-6 m RNA; (2) the expression of IL-1 alpha mRNA in C33A and increased IL-1 alpha mRNA level in the case of Me180 cells. Increased amounts of IL-6 mRNA were found in normal cells when treated with IL-1 alpha. In spit e of the pattern of mRNA expression, only HT-3 and normal cervical cel ls constitutively secreted IL-6, and only normal cells were able to pr oduce IL-1 alpha protein. A significant IL-la-dependent increase of IL -6 secretion was found in Me-180, HT-3 and normal cells. IL-1 alpha- a nd IL-6-driven cell proliferations were almost completely inhibited by the addition of neutralizing anti-IL-6 antibodies. Taken together, th ese data suggest that interleukins play a role in cervical carcinogene sis as autocrine and/or paracrine stimuli.