Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preterm labor associated with intrauterine infection is characterized by increased amniotic fluid concentrations of various proinflammatory cytokines, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage inflammatory protein-1alpha (MIP-1alpha). The purpose of this study was to determine if preterm labor in women with clinically evident chorioamnionitis is marked by elevations of the anti-inflammatory cytokine interleukin-4 (IL-4) and the T cell growth factor IL-2. Amniotic fluid samples were obtained from (1) women at term, not in labor (n = 10); (2) women at term, in labor (n = 10); (3) women with preterm contractions but undelivered within 1 week of amniotic fluid collection (n = 10); (4) women with preterm labor and delivery without clinically evident chorioamnionitis (n = 10); (5) women with preterm labor associated with chorioamnionitis (n = 8); and (6) women with preterm labor and delivery without infection matched with patients with chorioamnionitis (n = 8). Amniotic fluid concentrations of IL-4 and IL-2 were determined for each sample with a specific and sensitive enzyme-linked immunoassay. We found that women with infection-associated preterm labor and delivery had significantly higher concentrations of IL-4 when compared to appropriately matched controls (p < 0.05). Additionally, women with preterm labor and delivery not associated with infection had higher amniotic fluid IL-4 concentrations than women with preterm contractions but no labor (p < 0.05). Women with term labor had rare modest elevations of amniotic fluid IL-4. No IL-2 was detected in any sample. Our data indicate that amniotic fluid IL-4 is elevated in women with preterm labor and delivery, particularly in association with chorioamnionitis. We suggest that IL-4, although previously considered an anti-inflammatory agent, may have a paradoxical proinflammatory role in the pathogenesis of infection-associated preterm labor.
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PMID:Elevation of amniotic fluid interleukin-4 concentrations in women with preterm labor and chorioamnionitis. 896 Jun 15

Inflammatory cytokines seem to play a key role in mechanisms initiating labor. Since cytokine levels are higher in preterm than in term labor, it has been hypothesized that labor-inducing effects of cytokines are inhibited by an upregulated production of cytokine antagonists, such as soluble cytokine receptors, at early stages of gestation. In this study, TNF, IL-1, IL-6, IL-8 and soluble TNF receptors (sTNFRs) were measured in amniotic fluid samples from a) 39 women in premature labor, b) 25 women who where not in labor but delivered prematurely, and c) 33 women in term labor. Fifty-four of the placentas from premature deliveries were evaluated for presence of histological chorioamnionitis. Chorioamnionitis was associated with increased levels of TNF, IL-1 and IL-6, whereas elevated IL-1, IL-6 and IL-8 concentrations were found in premature parturition with no signs of infection. Concentrations of sTNFR were lower in preterm than in term deliveries. The present study confirms the participation of inflammatory cytokines in parturition. Multivariate analysis suggests a dominant, role of IL-1 in the presence of chorioamnionitis, whereas IL-6 seems to be more important during idiopathic premature labor. TNFR data do not support the hypothesis that production of cytokine antagonists is upregulated prematurely to prevent partirution.
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PMID:TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor. 959 63

Little is known about the mechanisms controlling the expression of key proteins that regulate excitability and contractility in the human myometrium at term. However, evidence is accumulating to suggest that the cytokine transforming growth factor (TGF)beta may play a central role. TGFbeta1 and TGFbeta receptors are present in the myometrial cells, indicative of an autocrine signaling system. Furthermore, the levels of TGFbeta1 and the expression of its receptors increase in the myometrium at term suggesting that they are, in turn, regulated and form part of a physiological cascade of events involving a number of autocrine signaling associated proteins. The present experiments were done to identify factors that regulate the expression of TGFbeta1 and TGFbeta receptors and may form other elements of this cascade. Because IL-1 and IL-8 are found in the myometrium at term and have been implicated in the etiology in premature labor we focus on this cytokines. Receptors for IL-1 and IL-8 were detected in the myometrial cells. Using Western blot analysis, the levels of expression were found to vary. The expression of IL-1 receptor type I was highest in the nonpregnant tissue with lower levels in nonlaboring myometrium with a further reduction in the spontaneously laboring tissue. In contrast, the expression of IL-8 receptor type B was highest in the pregnant nonlaboring tissue with a lower level in the spontaneously laboring tissue. Using an in vitro model, TGFbeta1 and TGFbeta receptor expression was up-regulated by IL-8, IL-1, and TGFbeta1 itself. However, IL-8 receptor expression was decreased by IL-8 and TGFbeta1. This suggests that in a cascade IL-8 would feed forward to promote the TGFbeta system, whereas TGFbeta1 feeds back to inhibit responsiveness to IL-8. Estrogen and progesterone increased the release of TGFbeta1. However, at high concentrations, estrogen and progesterone (100 nM 17beta-estradiol or 200 nM progesterone) decreased the level of TGFbeta receptor expression. Thus, the progressive rise of steroid levels in vivo might account for the observed changes in TGFbeta1 and TGFbeta receptor expression in vivo. Taken together, these observations support the idea that there is a cascade of autocrine signals that may play a major role in the physiological processes preparing the myometrium for parturition at term.
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PMID:Complex interactions between sex steroids and cytokines in the human pregnant myometrium: evidence for an autocrine signaling system at term. 1034 39

The effects of five inflammatory cytokines, i.e. interleukin(IL)-1alpha, IL-1beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) on prostaglandin E(2) (PGE(2)) production from amnion cells cultured in a serum-free condition was evaluated. After human amnion cells obtained from term placenta were incubated with the inflammatory cytokines at various concentrations, PGE(2) production in the culture supernatant was determined using an enzyme immunoassay method. Under a serum-free culture condition, an increase in PGE(2) production by IL-1alpha and IL-1beta was observed at concentrations of 10 and 100 ng/ml compared to control cultures. However, the increases in PGE(2) production by IL-6 and IL-8 were found at relatively high concentrations, i.e. at 100 and 200 ng/ml. TNF-alpha induced a significant increase in PGE(2) production at 50 and 100 ng/ml, but not at 200 ng/ml. These data suggest that these inflammatory cytokines directly stimulate PGE(2) production from amnion cells and may initiate premature labor if amniotic inflammatory cytokines are elevated, e.g. following intrauterine infection.
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PMID:Effects of inflammatory cytokines on prostaglandin E(2) production from human amnion cells cultured in serum-free condition. 1067 14

Preterm labor is associated with the release of various cytokines that play an important role in its pathophysiology. In preterm labor, tocolytics are used to inhibit uterine contractions and prolong gestation. We tested the hypothesis that tocolytics alter endotoxin-induced interleukin (IL-8) production from amniotic and decidual cells in vitro. Amniotic and decidual cells were isolated from patients undergoing elective repeat cesarean section at term. Cells were grown in tissue culture flasks. Cells were subsequently incubated with 100 ng/ml of endotoxin in 24 well plates in the presence of increasing concentrations of magnesium sulfate, nifedipine and terbutaline. After 24 h, IL-8 levels in each well were measured by ELISA. Endotoxin caused a significant elevation in IL-8 production in both amniotic and decidual cells. Magnesium sulfate dose dependently inhibited the endotoxin-stimulated IL-8 production in both decidual and amniotic cells. However, nifedipine and terbutaline did not significantly affect IL-8 production in either cell type. In conclusion, magnesium sulfate differentially suppresses endotoxin-stimulated IL-8 production in amniotic and decidual cells in vitro. The cellular mechanisms of this suppression and its clinical relevance in the setting of preterm labor merit further investigation.
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PMID:Effect of tocolytics on interleukin-8 production by human amniotic and decidual cells. 1638 5

Preterm labour (PTL) is the most important cause of neonatal morbidity and mortality. While some causes have been identified, the mechanisms involved remain elusive. This study investigates whether term labour (TL) is an appropriate model for PTL by examining pro-labour gene expression, using quantitative rtPCR, and protein synthesis, using Western analysis, in preterm and term myometrial samples obtained from the upper and lower uterine segments before and after the onset of labour. In the lower segment, the levels of prostaglandin H synthase type-2 (PGHS-2), interleukin-1beta (IL-1beta), IL-6 and IL-8 mRNA expression were significantly higher in TL compared with PTL samples. Compared with non-labour controls, the expression of IL-1beta and IL-8 mRNA was increased in both PTL and TL samples and the expression of PGHS-2 and IL-6 mRNA was increased in TL samples only. In the upper segment, there were no differences between PTL and TL samples and the mRNA expression of PGHS-2 and IL-1beta was increased in TL compared with term no labour samples. No effect of PTL or TL was seen on either oxytocin receptor or connexin-43 mRNA expression or protein levels. The multiple regression analysis and studies in primary cultures of uterine myocytes suggest that the inflammatory cytokines, IL-1beta and tumour necrosis factor-alpha, are the most important regulators of PGHS-2 and IL-8. Our data show that preterm and term labouring myometrium are significantly different and that the most marked labour-induced changes in gene expression are in the lower segment. These changes may occur in response to the release of inflammatory cytokines by the labour-associated inflammatory infiltration.
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PMID:Pro-labour myometrial gene expression: are preterm labour and term labour the same? 1836 15