European Journal of Pharmacology, 192 (1991) 189-191 © 1991 Elsevier Science Publishers B.V. (Biomedical Division) 0014-2999/91/$03.50 ADONIS 001429999100058G
189
EJP 20761
Short communication
Interleukin-6 stimulates prostaglandin production by human amnion and decidual cells M u r r a y D. Mitchell, D o n a l d J. D u d l e y , S a m u e l S. E d w i n a n d S a r a h L u n d i n Schiller Department of Obstetrics and Gynecology, University of Utah Medical Center, Salt Lake City, UT 84132, U.S.A. Received 6 November 1990, accepted 13 November 1990
The effects of interleukin-6 on prostaglandin production by cells from two key sources on intrauterine prostaglandin, i.e. arnnion and decidua, have been evaluated. Interleukin-6 induced a concentration-related increase in prostaglandin production by amnion and decidual cells. The concentrations of interleukin-6 required for this stimulatory action are within the range measured in amniotic fluid of women with intrauterine infections and preterm labor. Hence, interleukin-6 may contribute to the mechanism of preterm labor under these conditions. Interleukin-6; Prostaglandin biosynthesis; Amnion; Decidua; Labour
1. Introduction
2. Materials and methods
Prematurity remains the major cause of perinatal mortality and morbidity (Van den Berg and Oechsli, 1984). There is evidence that a significant proportion of preterm deliveries are associated with intrauterine infection and it has been proposed that the host response to infection may play a key role in the mechanism of preterm labor associated with intrauterine infection (Romero et al., 1988). This hypothesis holds that cytokines secreted as part of the host response, (particularly interleukin-1 and tumor necrosis factor) stimulate prostaglandin production by intrauterine tissues resulting in uterine contractions. Evidence for cytokine secretion and action on amnion and decidua has been presented (Romero et al., 1989; Mitchell et al., 1990). Recently, it has been shown that interleukin-6 is found in large amounts in amniotic fluid of women in preterm labor with clinical and laboratory evidence of intrauterine infection (Romero et al., 1990). We have, therefore, evaluated the effects of interleukin-6 on prostaglandin synthesis by amnion and decidua, the key sources of prostaglandin production during labor.
Placentas were obtained at elective repeat Cesarean sections, and amnion and decidua were separated by blunt dissection. Amnion and decidual cells were isolated and cultured as described previously (Okita et al., 1983; Mitchell et al., 1990). At confluence, cells were incubated with various concentrations of interleukin-6 ( R & D Systems, Minneapolis, MN) for 16 h and media collected. Cellular protein was determined by the method of Lowry et al. (1951). Prostaglandins E 2 and F2~ were measured by specific and sensitive radioimmunoassay directly in the culture media using an equivalent volume of culture media in the standard curve (Mitchell et al., 1990). The antisera was supplied by Advanced Magnetics Inc. (Cambridge, MA) and has negligible cross-reaction with interleukin-6. Statistical differences were assessed using Student's t-test.
Correspondence to: M.D. Mitchell, University of Utah Medical Center, Department of Obstetrics and Gynecology, Room 2B302, Salt Lake City, UT 84132, U.S.A.
3. Results
Interleukin-6 induced a concentration-related increase in prostaglandin production by both amnion and decidual cells. This occurred in all experiments from five individual amnions and decidua. Results from representative experiments are shown in figs. 1 and 2. For amnion cell prostaglandin E 2 production the increase was significant only at 100 n g / m l (P < 0.002). For decidual cell prostaglandin E 2 production the increase
190 12
.t:: to
10
c:
o
8
0.
~
6
c o
g
4
0_
N W
2
0_
Control
O. 1
1
Interteukin-6
10 ( ng/ml
100
)
Fig. 1. The effects of interleukin-6 on prostaglandin E 2 production by human amnion cells. For statistical differences see text.
was significant only at 10 and 100 n g / m l (P < 0.01 and P
189
EJP 20761
Short communication
Interleukin-6 stimulates prostaglandin production by human amnion and decidual cells M u r r a y D. Mitchell, D o n a l d J. D u d l e y , S a m u e l S. E d w i n a n d S a r a h L u n d i n Schiller Department of Obstetrics and Gynecology, University of Utah Medical Center, Salt Lake City, UT 84132, U.S.A. Received 6 November 1990, accepted 13 November 1990
The effects of interleukin-6 on prostaglandin production by cells from two key sources on intrauterine prostaglandin, i.e. arnnion and decidua, have been evaluated. Interleukin-6 induced a concentration-related increase in prostaglandin production by amnion and decidual cells. The concentrations of interleukin-6 required for this stimulatory action are within the range measured in amniotic fluid of women with intrauterine infections and preterm labor. Hence, interleukin-6 may contribute to the mechanism of preterm labor under these conditions. Interleukin-6; Prostaglandin biosynthesis; Amnion; Decidua; Labour
1. Introduction
2. Materials and methods
Prematurity remains the major cause of perinatal mortality and morbidity (Van den Berg and Oechsli, 1984). There is evidence that a significant proportion of preterm deliveries are associated with intrauterine infection and it has been proposed that the host response to infection may play a key role in the mechanism of preterm labor associated with intrauterine infection (Romero et al., 1988). This hypothesis holds that cytokines secreted as part of the host response, (particularly interleukin-1 and tumor necrosis factor) stimulate prostaglandin production by intrauterine tissues resulting in uterine contractions. Evidence for cytokine secretion and action on amnion and decidua has been presented (Romero et al., 1989; Mitchell et al., 1990). Recently, it has been shown that interleukin-6 is found in large amounts in amniotic fluid of women in preterm labor with clinical and laboratory evidence of intrauterine infection (Romero et al., 1990). We have, therefore, evaluated the effects of interleukin-6 on prostaglandin synthesis by amnion and decidua, the key sources of prostaglandin production during labor.
Placentas were obtained at elective repeat Cesarean sections, and amnion and decidua were separated by blunt dissection. Amnion and decidual cells were isolated and cultured as described previously (Okita et al., 1983; Mitchell et al., 1990). At confluence, cells were incubated with various concentrations of interleukin-6 ( R & D Systems, Minneapolis, MN) for 16 h and media collected. Cellular protein was determined by the method of Lowry et al. (1951). Prostaglandins E 2 and F2~ were measured by specific and sensitive radioimmunoassay directly in the culture media using an equivalent volume of culture media in the standard curve (Mitchell et al., 1990). The antisera was supplied by Advanced Magnetics Inc. (Cambridge, MA) and has negligible cross-reaction with interleukin-6. Statistical differences were assessed using Student's t-test.
Correspondence to: M.D. Mitchell, University of Utah Medical Center, Department of Obstetrics and Gynecology, Room 2B302, Salt Lake City, UT 84132, U.S.A.
3. Results
Interleukin-6 induced a concentration-related increase in prostaglandin production by both amnion and decidual cells. This occurred in all experiments from five individual amnions and decidua. Results from representative experiments are shown in figs. 1 and 2. For amnion cell prostaglandin E 2 production the increase was significant only at 100 n g / m l (P < 0.002). For decidual cell prostaglandin E 2 production the increase
190 12
.t:: to
10
c:
o
8
0.
~
6
c o
g
4
0_
N W
2
0_
Control
O. 1
1
Interteukin-6
10 ( ng/ml
100
)
Fig. 1. The effects of interleukin-6 on prostaglandin E 2 production by human amnion cells. For statistical differences see text.
was significant only at 10 and 100 n g / m l (P < 0.01 and P
