Distinct patterns of expression of interleukin-1 alpha and beta by normal and cancerous human ovarian tissues

Immunohistochemical staining of normal and cancerous ovarian tissues has demonstrated that both IL-1 alpha and IL-1 beta are more strongly expressed in cancerous than in normal tissues and are secreted mainly by epithelial cells. We have shown by bioassay and immunoassay that cancerous, but not normal ovarian tissues constitutively secrete IL-1 in vitro. Activation of cancerous ovarian tissues by lipopolysaccharide (LPS) increased its capacity to secrete IL-1. Normal ovarian tissues secreted low amounts of IL-1 only after prolonged stimulation (72-96 h) by high doses of LPS (10-100 micrograms/ml). On the other hand, constitutive IL-1 was detected in homogenates of normal ovarian tissues and stimulation by LPS increased its capacity to produce IL-1. IL-1 beta was the main type of IL-1 secreted by cancerous ovarian tissues. IL-1 alpha was detected at lower levels. In contrast, in normal tissues similar amounts of both IL-1 alpha and IL-1 beta were detected in the supernatants. The levels of both types of IL-1, and also the bioactivity of IL-1 were significantly higher in cancerous than in normal ovarian tissues. Established primary cell lines from normal ovarian tissues did not secrete IL-1 into supernatants but did express it at very low levels. Stimulation with LPS did not affect the capacity of these cell lines to secrete IL-1 but it increased their capacity to express it. In contrast, primary established epithelial cell lines from cancerous ovarian tissues did secrete and express high levels of IL-1 and these levels were increased under stimulation with LPS. Cancerous ovarian tissues did not only secrete higher levels of both IL-1 alpha and beta than normal ovarian tissues, but also the mechanism controlling the secretion of these factors in cancerous ovarian tissues seemed to be different from that found in normal ovarian tissues. Our results suggest that paracrine/autocrine factors may be involved in the regulation of both types of IL-1 secreted by ovarian tissues. These cytokines may play a role in regulating the physiological, pathophysiological and oncogenic processes of the ovary.