Effect of dehydroepiandrosterone sulfate on interleukin-8 receptor during cervical ripening.

We investigated the effects of dehydroepiandrosterone sulfate (DHA-S) on the production of interleukin-8 (IL-8) and expression of the interleukin-8 receptor (IL-8 R) in human cervical tissue. DHA-S increased the levels of IL-8 in cultured human cervical fibroblasts and in the supernatant in a time- and dose-dependent manner. DHA-S induced IL-8 and IL-8 R expression in human cervical fibroblasts and human pregnant cervical tissue at term in a dose-dependent manner. In addition, it induced the expression of IL-8 R in an explant culture of human cervical tissue and cultured human cervical fibroblasts in a time- and dose-dependent manner. However, dehydroepiandrosterone (DHA) only slightly induced the production of IL-8 and the expression of IL-8 R in the same cells and tissue. These results suggest that DHA-S up-regulates the autocrine system of IL-8 through the expression of IL-8 R.

Decreased renal and hepatic blood flow with preeclampsia-like histologic changes was obtained by stimulation of the celiac ganglion with LPS.

Decreased renal and hepatic blood flow with preeclampsia-like histologic changes was developed by stimulation of the celiac ganglion with lipopolysaccharide (LPS) in pregnant rabbits. The renal and hepatic blood flow were measured after stimulation of the celiac ganglion with 10 microL (group 1), 100 microL (group II) and 300 microL (group III) of LPS (10 mg/mL conc.) and with 100 microL of normal saline (group IV). The bifurcation of the abdominal aorta was also stimulated with 300 microL of LPS (group V). A control experiment was also done in this study (group VI). Histopathological studies of kidney and liver tissue were also performed in this protocol. A significant reduction in renal and hepatic blood flow was observed in pregnant rabbits with the times and dosage dependent on stimulation of the celiac ganglion by LPS. Stimulation of the bifurcation of the abdominal aorta with LPS could not produce any changes in renal and hepatic blood flow. Preeclampsia-like histologic changes of kidney and liver tissue were also observed. These results suggest that exogenous stimulation of the celiac ganglion causes decreased renal and hepatic blood flow, resulting in preeclampsia-like histologic changes of kidney and liver in pregnant rabbits.

Increased concentrations of plasma epinephrine and norepinephrine in patients with eclampsia.

We measured plasma catecholamine concentrations on admission (after eclamptic fit) and after 6 days of delivery in 21 eclamptic patients and on admission in 15 normotensive pregnant women in Bangladesh. Plasma epinephrine and norepinephrine concentrations in eclamptic patients were significantly higher on admission than those of normotensive pregnant women (P < 0.0001). Plasma catecholamine concentrations and mean arterial blood pressure had return to be almost normal as normotensive pregnant women after 6 days of delivery, resulting in no correlation between mean arterial blood pressure and plasma catecholamines. On admission (after eclamptic fit) mean arterial blood pressure was positively correlated with plasma epinephrine (r = 0.626, P < 0.002) and norepinephrine (r = 0.553, P < 0.008) concentrations in patients with eclampsia. The amount of proteinuria was also significantly correlated with plasma epinephrine (r = 0.515, P < 0.02) and norepinephrine (r = 0.606, P < 0.003) concentrations. Number of convulsions was significantly correlated with concentrations of plasma epinephrine (r = 0.514, P < 0.02), norepinephrine (r = 0.521, P < 0.01) and mean arterial blood pressure (r = 0.535, P < 0.01). A positive correlation was found between time passed after convulsion with plasma epinephrine (r = 0.515, P < 0.02) and norepinephrine (r = 0.570, P < 0.006) concentrations. These suggested that the increased plasma levels of epinephrine and norepinephrine in eclamptic patients were well correlated with the severity of the clinical features of eclampsia.

The role of hyaluronic acid as a mediator and regulator of cervical ripening.

During pregnancy, hyaluronic acid (HA) concentration in the human cervix is very low, but increases rapidly at the onset of labour. HA has a high affinity for water molecules and hence can maintain tissue hydration. HA can stimulate collagenase production in rabbit cervix, and also stimulates migration and function of polymorphonuclear leukocytes in the tissues. It is an endogenous regulator of interleukin-1 (IL-1). We hypothesized that HA plays an essential role during cervical ripening. The effect of exogenous application of HA (20 mg) on non-pregnant and pregnant (day 23) rabbit cervices was compared with controls. HA induced cervical ripening in both pregnant and non-pregnant animals, and cervical water content was significantly increased. Tissue collagen was markedly decreased. The localization and distribution of HA and HA receptor CD44 was determined in non-pregnant and pregnant human cervical connective tissue using biotinylated HA binding protein and CD44 monoclonal antibodies. Both were widely distributed in the connective tissues, especially around the blood vessels and cervical glands. The effect of IL-8 (50, 100, 150 and 200 ng/ml) on HA production and hyaluronidase (HAase) activity was investigated in cultures of lower uterine segment collected during elective Caesarean sections. HA production was stimulated in a dose-dependent manner; there was no effect on hyaluronidase activity. HA administration (0.5, 1 and 2 mg/ml) stimulated the activities of collagenase and gelatinase together with IL-8 production in the culture supernatants. Thus HA may play an important role in cervical ripening, being involved in the regulation of cervical tissue water content, collagenolytic enzymes and cytokines.

Experimental hemolytic uremic syndrome induced by lipopolysaccharide irritation of celiac ganglia in rats.

Although nervous system complications often appear in hemolytic uremic syndrome (HUS), the relationship between HUS and the nervous system is still not clear. We suspect that damage to the nervous system may play a role in the pathophysiology of HUS. In this context, rats received different doses of lipopolysaccharide (LPS) or saline to celiac ganglia or peritoneum. In rats treated with LPS on the celiac ganglia, a significant decrease in platelet count (p < 0.05) and a significant increase in blood urea nitrogen (p < 0.05) were found, and at the same time plasma levels of adrenaline and noradrenaline increased markedly (p < 0.05). The renal arterioles and glomeruli showed endothelial swelling and narrowing of the lumina. Intense immunostaining for von Willebrand factor and fibrinogen in glomeruli and renal vessels was also observed. These parameters were accompanied by a systolic blood pressure elevation. The results suggest that the sympathetic nervous system plays an important role in the pathogenesis of HUS.

Hypolumbarlordosis: a predisposing factor for preeclampsia.

OBJECTIVE: The aim of this research was to study the relationship between lumbar lordosis and preeclampsia. STUDY DESIGN: We studied lumbar lordosis of 52 primipara patients with pregnancy-induced hypertension and 59 normal primipara pregnant women. We determined the lumbar lordotic deviation (LLD) from lumbar lordosis measurement device in the lateral recumbent position and standing position. Roll-over test was performed for both groups. Resistance index (RI) of internal iliac artery was also measured by color Doppler sonography. RESULTS: The LLD was 33 +/- 6.1 degrees week 20-29 and 34 +/- 6.9 degrees week 30-40, respectively. In patients with preeclampsia, the LLD was 19.8 +/- 6.3 degrees week 20-29, 21.3 +/- 7.9 degrees week 30-40. The LLD in patients with preeclampsia was significantly lower than in the normal pregnant women. The LLD correlated to the increase diastolic pressure after roll-over test significantly. Hypolumbarlordosis was frequently associated with high resistance of peripheral vessel. CONCLUSIONS: We conclude that hypolumbarlordosis is frequently associated with preeclampsia. It is also closely related to the mechanism for positive roll-over test and increase of resistance of vessels. As lumbar lordosis does not change greatly in individuals before pregnancy, hypolumbarlordosis may be a predisposing factor for preeclampsia.

Increased concentrations of plasma epinephrine and norepinephrine in patients with eclampsia.

We measured plasma catecholamine concentrations on admission (after eclamptic fit) and after 6 days of delivery in 21 eclamptic patients and on admission in 15 normotensive pregnant women in Bangladesh. Plasma epinephrine and norepinephrine concentrations in eclamptic patients were significantly higher on admission than those of normotensive pregnant women (P < 0.0001). Plasma catecholamine concentrations and mean arterial blood pressure had return to be almost normal as normotensive pregnant women after 6 days of delivery, resulting in no correlation between mean arterial blood pressure and plasma catecholamines. On admission (after eclamptic fit) mean arterial blood pressure was positively correlated with plasma epinephrine (r = 0.626, P < 0.002) and norepinephrine (r = 0.553, P < 0.008) concentrations in patients with eclampsia. The amount of proteinuria was also significantly correlated with plasma epinephrine (r = 0.515, P < 0.02) and norepinephrine (r = 0.606, P < 0.003) concentrations. Number of convulsions was significantly correlated with concentrations of plasma epinephrine (r = 0.514, P < 0.02), norepinephrine (r = 0.521, P < 0.01) and mean arterial blood pressure (r = 0.535, P < 0.01). A positive correlation was found between time passed after convulsion with plasma epinephrine (r = 0.515, P < 0.02) and norepinephrine (r = 0.570, P < 0.006) concentrations. These suggested that the increased plasma levels of epinephrine and norepinephrine in eclamptic patients were well correlated with the severity of the clinical features of eclampsia.

Expression of interleukin-8 receptors in the gestational tissues before and after initiation of labor: immunohistochemical study.

BACKGROUND: Interleukin-8 (IL-8) has an essential role in the mechanism of parturition. IL-8 induces its effect through specific cell binding receptors. The main purpose of this research was to elucidate the presence of IL-8 receptors in the gestational tissues and their relation to parturition. MATERIALS AND METHODS: Fetal membranes, placenta, umbilical cord and myometrial samples were collected before the initiation of labor during elective Cesarean sections (n = 15). Similar biopsies (except myometrial samples) were also gathered after normal vaginal delivery (n = 15). Immunohistochemical staining for IL-8 receptors type I and II was carried out for the fresh frozen sections of all samples. Immunoreactive score (IRS) was calculated for the stained sections. RESULTS: IL-8 Receptors type I and II were recognized in the fetal membranes, placenta, umbilical cord and myometrial samples collected from patients before the initiation of labor. The staining of amnion and placentas were found to be more intensified in the samples collected after vaginal delivery compared to those from elective cesarean sections and before initiation of labor. CONCLUSIONS: Increased expression of IL-8 receptors after initiation of labor may indicate that IL-8 receptors might have a role during parturition.

Urinary trypsin inhibitor: a new drug to treat preterm labor: a comparative study with ritodrine.

UNLABELLED: Prevention of preterm delivery is one of the difficult problems facing obstetricians. beta Adrenergic agonists, especially ritodrine, are commonly used in these cases. OBJECTIVES: The aim of this research was to study and compare the effect of urinary trypsin inhibitor (UTI) which has anti-inflammatory anti-cytokine effects with ritodrine in treating preterm labor. STUDY DESIGN: Patients in preterm delivery were randomly selected to be treated either by ritodrine or UTI. In the ritodrine group, uterine contractions were initially suppressed by high doses of ritodrine (up to 300 micrograms/min) and then a maintenance dose was given until 35 weeks of gestation. In the UTI group one vaginal suppository (5000 U) was used daily for 2 weeks. Patients with recurrent preterm uterine contraction during the initial 14 days of treatment, who needed course of other drugs to suppress the contractions, were excluded from the study. Patients responding to the drugs were followed until delivery. Tocolytic index and elastase concentration in the cervical mucus was calculated. Recurrence rate of uterine contraction and time of elongation of pregnancy since the beginning of treatment was calculated. RESULTS: UTI was more effective than ritodrine in inhibition of recurrent uterine contraction and elongation of pregnancy. No side effects could be observed after treatment with UTI for the mother or the fetus. CONCLUSION: UTI may be a new therapeutic method for the inhibition of preterm delivery through suppression of cytokines and inflammatory mediators.

Biochemical changes in the cervical tissue of rabbit induced by interleukin-8, interleukin-1beta, dehydroepiandrosterone sulphate and prostaglandin E2: a comparative study.

The aim of this research was to study and compare the mechanism of action of interleukin (IL)-8, IL-1beta dehydroepiandrosterone sulphate (DHEA-S) and prostaglandin (PG)E2 on the cervix. Five equal groups of pregnant rabbits (n = 45) were tested by either placebo or tested drugs in the form of vaginal suppositories once daily for 3 days. The suppositories contained human recombinant IL-8 (100 ng), IL-1beta (200 ng), DHEA-S (10 mg) or PGE2 (1 mg). All rabbits were tested by one dose, two doses or three doses. Consistency, dilatation and water contents were estimated 24 h after the last dose of treatment. Leukocyte infiltration of the cervices was studied after staining the cervical tissue sections with antirabbit RT2 monoclonal antibodies. Relative collagen concentration was assessed after staining with Picrosirius Red. Collagenase, gelatinase and elastase activities were measured in 100 mg of homogenized cervical connective tissue. Water contents were significantly increased in all tested cervices. Neutrophil numbers were increased in IL-8 and IL-1beta groups after the second dose of treatment (P < 0.0005 and 0.001 respectively). In the PGE2 group, neutrophils were increased after the third dose of treatment, whereas in DHEA-S group no significant changes were observed. Collagen content was significantly decreased in IL-8, IL-1beta and PGE2 groups after the first dose of treatment (P < 0.004, and 0.005 and 0.03 respectively). In the DHEA-S group, the decrease in collagen content occurred after the third dose (P < 0.05). Collagenase activity was markedly increased in IL-8, IL-1, and DHEA-S groups after the second dose of treatment (P < 0.001, 0.003 and 0.007 respectively). No significant increase in collagenase activity was found in PGE2 group. Gelatinase activity was significantly increased in IL-8, IL-1beta, PGE2 and DHEA-S groups after the second dose of treatment (P < 0.008, 0.01, 0.003 and 0.05 respectively). Also, elastase activity was increased after the second dose of treatment in all groups (P < 0.001, 0.001, 0.001 and 0.006 respectively). Our data suggest that ripening of the cervix in rabbit can be initiated by different mechanisms. Cytokines play a vital role in cervical ripening, especially IL-8 and IL-1. IL-8 is one of the factors which could ripen the cervix in a manner similar to the physiological process at term.

Biochemical changes in the cervical mucus after application of laminaria tent.

BACKGROUND: This research was aimed to study the biochemical changes in cervical mucus after application of laminaria tent. MATERIAL AND METHODS: Cervical mucus was collected before and after insertion of laminaria tent from 20 normal pregnant women in the first and second trimesters. Interleukin-1 beta, IL-8, collagenase activity, elastase activity, PGE2 and PGF2 alpha were measured in the collected samples. Laminaria tent was also inserted in one vaginal cervix of five non-pregnant rabbits and the clinical and histological changes were compared with five non-treated rabbits. Collagen contents were assessed histologically and Leukocyte number was counted. RESULTS: IL-1 beta and IL-8 and elastase activity were significantly increased after insertion of laminaria (p<0.0001 and 0.001 respectively). Collagenase activity was not significantly changed. Whereas concentration of PGE2 and PGF2 alpha in the mucus were markedly increased (p<0.0001 and 0.001 respectively). Collagen contents were significantly decreased in laminaria and opposite side cervices (p<0.0001). No significant changes in leukocyte count could be observed in treated and non treated cervices. CONCLUSIONS: Insertion of laminaria leads to increase concentration of IL-1 beta, IL-8, PGE2, PGF2 alpha and elastase activity. Mechanical stretching of the cervix and biochemical changes in cervical mucus may explain the mechanism of cervical ripening induced by laminaria.

Effects of urinary trypsin inhibitor on myometrial contraction in term and preterm deliveries.

The aim of this research was to study the concentration of urinary trypsin inhibitor in amniotic fluid (AF) and its effect on myometrial contraction in term and preterm deliveries. Urinary trypsin inhibitor was measured in AF of term and preterm labor. Immunohistochemical staining of amnion and myometrium was carried out. Isometric uterine contraction was studied to elucidate the effect of AF and urinary trypsin inhibitor on the contractile activity of term and preterm myometrium. The effect of urinary trypsin inhibitor on the production of prostaglandin E2 (PGE2) from myometrial cultures stimulated by IL-8, IL-1 and LPS was verified. Urinary trypsin inhibitor was significantly increased in AF of cases of preterm delivery (p < 0.0001). Amnion and myometrium of preterm deliveries were faintly stained for urinary trypsin inhibitor compared to term delivery. Amniotic fluid and urinary trypsin inhibitor could successfully inhibit-myometrial contraction. Also, urinary trypsin inhibitor could significantly inhibit the production of PGE2 in the myometrial cell cultures stimulated by IL-1 and LPS (p < 0.001 and 0.0005). IL-8 has no significant effect on PGE2 production from myometrial cell culture. Urinary trypsin inhibitor suppresses myometrial contraction in term and preterm deliveries. It may play a role in maintaining normal pregnancy and preventing preterm delivery.

Immunohistological study in cases of HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) and acute fatty liver of pregnancy.

We immunohistologically studied the hepatic tissue sections in cases with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome; n = 2) and acute fatty liver of pregnancy (AFLP; n = 2) compared to necropsy controls. Unlike in the AFLP cases, a marked infiltration of neutrophils in liver tissues was found in both cases of the HELLP syndrome. Immunostaining with the antihuman (polyclonal) TNF-alpha, IL-1 beta, IL-8 and antihuman neutrophil elastase (monoclonal antibody) was performed in paraffin-embedded hepatic tissue sections. Liver tissues in HELLP syndrome patients were stained strongly with TNF-alpha and neutrophil elastase antibody. The strongest staining pattern was observed in the eclamptic case, whereas in the AFLP cases, as in the necropsy controls, a very weak staining for anti-TNF-alpha and elastase antibody was found. The liver sections of the HELLP syndrome cases were moderately stained with polyclonal IL-1 beta and IL-8 antibodies whereas AFLP and controls had a very faint staining. Significant correlations were found between the numbers of necrotic hepatocytes and elastase dots in the same microscopic fields (randomly selected) of liver sections from two cases of HELLP syndrome (r2 = 0.63; p < 0.0001), which might suggest a neutrophil-mediated tissue damage in such a disease. This study suggests that a cytokine- and neutrophil-mediated liver injury occurs in the HELLP syndrome but not in AFLP.

Correlated plasma elastase and sera cytotoxicity in eclampsia. A possible role of endothelin-1 induced neutrophil activation in preeclampsia-eclampsia.

The activation of neutrophils was studied in preeclampsia (n = 10) and eclampsia (n = 20) compared to normotensive controls (n = 10) and nonpregnant essential hypertensives (n = 10). Plasma elastase levels were raised in preeclampsia (0.53 +/- 0.32 microgram/mL, P < .002) and eclampsia (1.26 +/- 0.8 microgram/mL, P < .001) respectively compared to normal pregnancies (0.032 +/- 0.009 microgram/mL). The plasma elastases were more elevated in eclamptic cases compared to essential hypertensive (0.53 +/- 0.27 microgram/mL; P = .01) patients. We analyzed the correlation among elastase values, systolic (SBP), mean blood pressures (MBP), endothelin-1 (ET-1) levels and sera cytotoxicity (as measured by fura-2 release from human umbilical venous endothelial cell culture) in eclamptic cases. SBP and MBP were significantly correlated with plasma elastase levels in preeclampsia (r = 0.67, 0.63, respectively; P < .03) and eclampsia (r = 0.49, 0.49, respectively; P < .02). ET-1 levels were correlated with SBP (P = .003) and MBP (P = .001) and corresponding elastase levels (r = 0.606, P < .003) in eclamptic patients. Doses of 10, 25, and 50 pmol/mL of ET-1 increased elastase release in human neutrophil cultures dose and time dependently. Cytotoxicity of eclamptic sera correlated (P < .001) to the corresponding plasma elastase values. Therefore, this study suggests that neutrophil activation and ET-1 induced neutrophil activation occurs in this disease.

Plasma P selectin (GMP-140) and glycocalicin are elevated in preeclampsia and eclampsia: their significances.

OBJECTIVE: We measured the concentrations of plasma P selectin (or GMP-140) and glycocalicin in preeclamptic and eclamptic women. Correlations between these two parameters and blood pressures, platelet counts, or plasma thrombin-antithrombin complex values were evaluated. STUDY DESIGN: By use of enzyme-linked immunosorbent assays we measured the plasma GMP-140 and glycocalicin levels in normal pregnancies (n = 10) and preeclamptic (n = 10) and eclamptic (n = 20) pregnancies. The glycocalicin index was calculated as follows: (glycocalicin x [250 x 10(6)/ml])/(Individual platelet counts). Correlations between plasma GMP-140, glycocalicin, glycocalicin index values, blood pressures, platelet counts, and plasma thrombin-antithrombin complex values were analyzed. RESULTS: Plasma GMP-140 levels were found to be significantly elevated in preeclamptic (p < 0.0005) and eclamptic cases (p < 0.0001) compared with normotensive controls. Plasma glycocalicin (p = 0.01, 0.007) and glycocalicin index (p = 0.005, 0.002) values were also markedly elevated in preeclamptic and eclamptic patients compared with normal pregnant patients. Significant correlations between platelet counts or plasma thrombin-antithrombin complex levels and their corresponding plasma GMP-140 and glycocalicin and glycocalicin index values have been found in preeclamptic and eclamptic cases. However, blood pressures had correlations with GMP-140, glycocalicin, and glycocalicin index values in eclamptic cases. CONCLUSIONS: We demonstrated an elevation of plasma GMP-140 and platelet glycocalicin in preeclampsia and eclampsia. This study also reflects the usefulness of glycocalicin as a marker of platelet activation or turnover and endothelial dysfunction in these diseases.

Endothelin-1 evoked an increase and oscillations in cytosolic calcium concentration in adherent single human platelets and increased GMP-140 (P-selectin) in platelet suspension.

The effect of endothelin-1 (ET-1) on cytosolic calcium ion concentration ([Ca2+]i) in adherent single human blood platelet was determined by fluorescence digital imaging microscopy using Fura-2 as calcium probe. A dose dependent increase and oscillatory changes in [Ca2+]i in single platelets were evoked by ET-1 as with thrombin. Half and 1 microM of ET-1 increased (p < 0.01) the [Ca2+]i in single platelets from a resting level of 83 +/-3.4 nM to 120 +/- 13 nM and 240 +/- 20 nM respectively. The ET-1 induced increase in [Ca2+]i was suppressed by 1 mM EGTA, a calcium chelating agent in the medium. ET-1 increased the production of IP3 (quantitified by IP3 3H-radioreceptor assay kit) in platelets significantly (p < 0.05) in a dose dependent way. We measured the GMP-140 (P-selectin) level in the supernatant of human platelet suspensions incubated with thrombin and ET-1. Both thrombin and ET-1 increased the secretion of soluble GMP-140 in the supernatant of platelet suspensions. Therefore, we suggested that ET-1 increased [Ca2+]i in platelets by both calcium influx and IP3 mediated Ca2+ release resulting in activation and release of GMP-140.

Urinary trypsin inhibitor prevents uterine muscle contraction by inhibition of Ca++ influx.

OBJECTIVE: The aim of this research was to elucidate the mechanism of action of urinary trypsin inhibitor, a Kunitz-type protease inhibitor, in suppressing uterine muscle contraction. STUDY DESIGN: An isometric uterine contraction test was used to study this inhibitory effect of urinary trypsin inhibitor on the myometrium. Oxytocin, prostaglandin F2 alpha, and lipopolysaccharide were used to stimulate myometrial contraction. Prostaglandins F2 alpha and E2 were measured in the buffer solution. Influx of calcium into uterine smooth muscle cells was assessed by digital imaging microscopy. RESULTS: After incubation with urinary trypsin inhibitor or fetal urine, myometrial contractions stimulated by oxytocin, prostaglandin F2 alpha or lipopolysaccharide were suppressed completely. The concentrations of prostaglandins F2 alpha and E2 in the buffer solution during the isometric contraction test were significantly increased by lipopolysaccharide stimulation, but when urinary trypsin inhibitor was present in the buffer solution the concentrations of prostaglandins F2 alpha or E2 did not change significantly. Preincubation with urinary trypsin inhibitor also inhibited calcium influx, resulting in no detectable change in the intracellular free calcium concentration of smooth muscle cells. CONCLUSION: We proposed that urinary trypsin inhibitor from fetal urine inhibits uterine muscle contraction by regulation of intracellular Ca++.

Regulatory effect of aminopeptidase inhibitor (bestatin) on the cervix during induction of ripening by interleukin-8.

Bestatin is an immunomodulatory peptide that stimulates the humoral and cell-mediated immune system. It also has an inhibitory effect on multiple aminopeptidases. Recently we found that aminopeptidase N inactivates interleukin-8 in vitro. Bestatin successfully suppresses the effect of aminopeptidase N on interleukin-8. During cervical maturation many biochemical changes occur including decrease in collagen concentration and increase in collagenase and elastase activities. Interleukin-8, which has a potent neutrophil chemotactic effect, was found to induce cervical ripening in rabbits. The combination of interleukin-8 with bestatin also induced cervical ripening by providing approximately regular levels of neutrophil numbers, collagenase, and elastase activities. We therefore suggest that this regulatory mechanism also takes place in vivo through the inhibitory effect of bestatin on aminopeptidase N.

Urinary trypsin inhibitor suppresses premature cervical ripening.

UNLABELLED: Unknown signals from the fetus are thought to be involved in the onset of parturition. We recently discovered that urinary trypsin inhibitor (UTI) from fetal urine inhibits uterine muscle contraction. OBJECTIVES: The aim of this research was to elucidate the mechanism of action of UTI in suppressing cervical maturation. STUDY DESIGN: Non-pregnant and pregnant rabbits pretreated with and without UTI suppositories containing 1000 U (400 micrograms) for 3 days were treated for 2 days with vaginal suppositories containing 100 ng of interleukin-8 (IL-8). RESULTS: IL-8 induced softening and dilatation of the rabbit cervices. In contrast UTI inhibited IL-8 induced cervical softening and dilatation. Water content, collagen content, neutrophil counts, elastase activity and collagenase activity of the cervix were increased by IL-8, but they did not increase by IL-8 with UTI. CONCLUSION: These results suggest that UTI inhibits cervical maturation induced by IL-8.

The effect of interleukin-1 in rabbit cervical ripening.

OBJECTIVE: In this research we studied the effect of interleukin-1 beta (IL-1 beta) on the cervix. STUDY DESIGN: Vaginal suppositories of a low dose of IL-1 beta (200 ng) were applied to non-pregnant and pregnant rabbits. Results were compared with a control group which were treated only by placebo. Water concentration, collagen content, collagenase and elastase activities were measured. Neutrophil numbers in the cervical connective tissue were counted. Also, interleukin-8 (IL-8) was measured in the supernatant of homogenized cervical tissue treated by IL-1 beta. RESULTS: Water contents of the tested cervices were increased (P < 0.006 and 0.03, respectively), whereas collagen content was markedly decreased (P < 0.0004 and 0.001, respectively). Collagenase activity was found to be increased in non-pregnant and pregnant cervices treated by IL-1 beta (P < 0.02 and 0.002, respectively). Also, elastase activity of these cervices were significantly increased compared to the control group (P < 0.0007 and 0.001, respectively). Neutrophil invasion was observed in the cervical connective tissues after application of IL-1 beta. IL-8 was significantly elevated (P < 0.0001) in the treated cervices. CONCLUSION: Interaction between IL-1 and IL-8 is suspected to be essential for cervical ripening.