In all animals except one, increases in amniotic fluid concentrations of IL-1 (3 and TNFa preceded the decreases in amniotic fluid prolactin (Table 1). An increase in PGE2 also preceded the decrease in prolactin (Table 2). Progesterone levels in the amniotic fluid, maternal artery, and fetal vein were higher at the onset of labor (after infection) than prior to infection, indicating that the decrease in prolactin was not due to a decrease in progesterone in any of these compartments (Table 3). The progesterone, IL-1 p, TNFa, and PGE2 concentrations resulting from the intraamniotic inoculations were reported earlier in a different format and are presented here to facilitate comparison.
A brief infusion of IL-ip also caused a decrease in amniotic fluid prolactin that was followed by labor in 5 of 6 animals. In the case in which labor did not occur, amniotic fluid prolactin then returned to normal after 4 days (n = 1). Figure 4A shows results for a representative animal that was infused with 10 |xg of IL-1 (3. Delivery at night ensued 2.5 h after the last sample. The prolactin levels of the 6 animals were stratified into three time periods for statistical analysis, and the results are shown in Figure 5, A and B. There was a significant decline in prolactin immediately after infusion that was maintained to 72 h. These results are similar to the results obtained with intraamniotic bacterial infection. buy asthma inhalers
In the animals from which the prolactin levels were obtained, there was a 2-fold increase in PGE2 from 3.5 ± 2.6 to 7.2 ± 2.8 ng/ml (p < 0.05). In addition, there was an increase in uterine activity at 6.0 ± 2.45 h from infusion. Five of the six animals delivered at 73.8 ± 28.8 h after infusion, and one animal delivered 8 days after infusion.
IL-1 fi Plus Indomethacin
Administration of indomethacin together with IL-ip prevented the increase in PGE2 that was observed with infusion of IL-ip alone. PGE2 levels were 0.20 ± 0.08 ng/ml prior to infusion of indomethacin and 0.35 ± 0.02 ng/ml (not different) during coadministration of indomethacin and IL-1 p. Hence, indomethacin prevented the increase in uterine activity and preterm labor that was associated with infusion of IL-1(3 alone. Figure 4B depicts a representative animal given 10 |xg of IL-lp and indomethacin.
TABLE 1. Amniotic fluid (AF) prolactin and experimental intraamniotic infection.
|Animal #||Inoculum||Innoc. day of gestation||Time following infection until:|
|Increases in uterine contractility||Delivery||Increases in AFTNFct||Increases in AF IL-1 p||Decline in AF prolactin|
|12283||10‘ GBS||132||32 h||50 h||22 h||22 h||12 h|
|11925||106 GBS||132||14 h||72 h||12 h||12 h||12 h|
|9836||106 GBS||126||40 h||53 h||6 h||22 h||39 h|
|11067||103 GBS||137||50 h||62 h||8 h||24 h|
|14685||10» GBS||148||27 h||41 h||18 h||24 h|
* Heat-inactivated 106 GBS.
TABLE 2. Mean amniotic fluid prolactin, IL-10, and PGE2 concentrations following experimental intraamniotic or choriodecidual infection in rhesus monkeys.
|Prolactin ((j-g/ml)||034.0||1-12 h 33.9||13-24 h 22.5||Time following 25-36 h 22.0||infection 37-48 h 20.3||49-60 h 13.1*||61-72 h 9.7*|
|IL-1 |J (pg/ml)||25||190||1072*||1734*||2142*||2037*||1848*|
|Number of animals||6||6||6||6||6||4||3|
* Significantly different from Time 0 at p < 0.05 (ANOVA and Duncan’s pairwise comparison).
TABLE 3. Amniotic fluid prolactin and progesterone concentrations before infection (basal) and following the onset of labor in rhesus monkeys (data presented as median and range in parentheses).
|Prolactin||Amniotic||41.9 (13.0-47.1)||8.8 (2.2-30.4)*|
|Progesterone||Amniotic||0.04 (0.03-0.07)||0.20 (0.05-2.05)*|
|Maternal||2.6 (1.5-3.9)||5.5 (2.3-13.1)*|
|Fetal vein||2.6 (1.6-5.8)||8.8 (2.4-14.9)*|
* p < 0.05, Mann-Whitney U test.