Interleukin 8 production and interleukin 8 receptor expression in human myometrium and leiomyoma

OBJECTIVE: Interleukin 8 is a potent chemoattractant cytokine that is expre ssed in a variety of human tumors and is known to induce mitogenesis. We ai med to investigate the production of interleukin 8 and the expression of it s receptor in myometrium and leiomyoma, in which we hypothesized that inter leukin 8 may contribute to cellular proliferation. STUDY DESIGN: Myometrial and leiomyoma tissue pairs (n = 14) were obtained from human uteri after hysterectomy conducted for leiomyomatous uterus. Exp ression of interleukin 8 and interleukin 8 receptor type A was identified i n the leiomyomatous myometrium by means of specific antibodies directed aga inst interleukin 8 and interleukin 8 receptor type A for immunohistochemica l detection. Interleukin 8 production by cultured cells was measured by enz yme-linked immunosorbent assay. The regulation of interleukin 8 messenger r ibonucleic acid expression was assessed by means of the Northern blot analy sis after treatment of myometrial cells with interleukin 1 alpha and tumor necrosis factor alpha. Myometrial cell proliferation was determined by mean s of colorimetric assay after cells were treated with interleukin 8 and ant ihuman interleukin 8 neutralizing antibody RESULTS: Immunostaining for both interleukin 8 and interleukin 8 receptor t ype A was stronger in the myometrium adjacent to leiomyoma compared with le iomyoma itself (2-fold, P <.05). Compared with samples from nonusers, sampl es from patients who had used gonadotropin-releasing hormone agonists revea led a trend for decreased staining for both interleukin 8 and interleukin 8 receptor type A. Interleukin 1<alpha> and tumor necrosis factor alpha caus ed a time- and dose-dependent increase in interleukin 8 production by myome trial cells (P <.001). There was a dose-dependent inhibition of cell prolif eration with antihuman interleukin 8 antibody to 55% of the control (P <.00 1). CONCLUSION: Our demonstration of high levels of interleukin 8 and its recep tor in myometrium immediately surrounding leiomyoma and the inhibition of c ell proliferation when interleukin 8 is blocked by a neutralizing antibody suggest a potential role for interleukin 8 in the growth of myometrial tiss ue surrounding leiomyomatous tissue. This study could lead to a better unde rstanding of potential involvement of cytokines in leiomyoma growth and in gonadatropin-releasing hormone agonist-induced regression.