The Influence of Interleukin (IL)-1β and IL-6 and Tumour Necrosis Factor-α on Prostaglandin Secretion from Porcine Myometrium during the First Third of Pregnancy

The present study was undertaken to determine the effect of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) on prostaglandin (PG)F-2 alpha and PGE(2) secretion as well as cyclooxygenase-2 (COX-2) protein expression in myometrium collected on days 25, 30 and 40 of pregnancy in pigs. Myometrial slices were incubated for 16 h with IL-1 beta, IL-6 and TNF-alpha (1 or 10 ng/ml of medium) or two combinations of the three cytokines (1 or 10 ng/ml of each cytokine per combination). We demonstrated the stimulatory effect of IL-1 beta and IL-6 on PGF(2 alpha) and PGE(2) secretion from myometrium collected on all examined days of pregnancy, excepting of influence of IL-6 on release of PGF(2 alpha) by tissue from day 30. In turn, TNF-alpha was able to stimulate only PGE(2) secretion by myometrium of 40-day-pregnant gilts. The three cytokines applied in combination augmented release of PGE(2) from myometrium collected on days 30 and 40 of pregnancy. Stimulation of PGE(2) secretion by cytokines used individually was more frequent than that of PGF(2 alpha). Moreover, an enhancement in PGF(2 alpha) and/or PGE(2) release was accompanied by an increase of COX-2 protein expression. Our study shows the ability of cytokines to stimulate PGF(2 alpha) and PGE(2) release by porcine myometrium from the first third of pregnancy. Obtained data suggest that locally PGs produced in myometrium influencing the uterine contraction activity may be important for the maintenance of myometrial quiescence during pregnancy and confirm also that the complex cytokine network is an important regulatory mechanism of PGs production during pregnancy.