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 growth factor (EGF) were tested for their ability to regulate epithelial cervical cell cytokine production and secretion and to induce proliferation of human normal and neoplastic epithelial cervical cells. IL-1 alpha, and IL-6 enhanced tumour and normal cell growth by 20-120%. The 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)-infected and HPV-non-infected cervical cells. Normal cells constitutively expressed IL-1 alpha, IL-6 and EGF mRNA. All cell lines except C33A expressed IL-1 alpha mRNA. CaSki, C-411 and HT-3 expressed mRNA for IL-6. IL-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 mRNA; (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 spite of the pattern of mRNA expression, only HT-3 and normal cervical cells constitutively secreted IL-6, and only normal cells were able to produce 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- and IL-6-driven cell proliferations were almost completely inhibited by the addition of neutralizing anti-IL-6 antibodies. Taken together, these data suggest that interleukins play a role in cervical carcinogenesis as autocrine and/or paracrine stimuli.