Differential release of interleukin-6 from human gestational tissues in association with labour and in vitro endotoxin treatment

1996 ◽  
Vol 149 (3) ◽  
pp. 431-439 ◽  
Author(s):  
N Laham ◽  
S P Brennecke ◽  
K Bendtzen ◽  
G E Rice
Keyword(s):  
Amniotic Fluid ◽  
Interleukin 6 ◽  
Elective Caesarean Section ◽  
Fold Increase ◽  
Dependent Manner ◽  
Explant Cultures ◽  
Gestational Tissues ◽  
Term Labour ◽  
Labour Onset

Abstract In this study, we quantified interleukin-6 (IL-6) concentrations in amniotic fluid at term and preterm labour, and determined the gestational tissue source of IL-6. In addition, aspects of the regulatory mechanisms involved in IL-6 release at the time of term labour and in response to bacterial endotoxin, lipopolysaccharide (LPS), have been established. IL-6 concentrations were 2-fold higher in amniotic fluid collected at term compared with preterm gestation, with an additional 2-fold increase in association with term labour. IL-6 was released from all choriodecidual and placental explants but was detected in only 33% of amniotic explant cultures of tissues obtained before labour onset. In contrast, IL-6 was detected in all amniotic, choriodecidual and placental cultures of tissues obtained after term labour onset and delivery, and the mean IL-6 release was significantly higher than that measured in explant cultures of both amniotic (80-fold increase, P<0·0001) and choriodecidual (3-fold increase, P<0·02) but not placental explants taken at the time of elective Caesarean section at term before labour onset. LPS significantly (P<0·05) increased the release of IL-6 from human choriodecidual and placental explants but not amniotic explants, in a time- and dose-dependent manner. IL-6 is a physiological constituent of amniotic fluid and its production by gestational tissues is differentially regulated by LPS and spontaneous labour onset and delivery. Journal of Endocrinology (1996) 149, 431–439

Labour-associated increase in interleukin-1 α release in vitro by human gestational tissues

1996 ◽  
Vol 150 (3) ◽  
pp. 515-522 ◽  
Author(s):  
N Laham ◽  
S P Brennecke ◽  
K Bendtzen ◽  
G E Rice
Keyword(s):  
Amniotic Fluid ◽  
Time Course ◽  
Interleukin 1 ◽  
Maternal Plasma ◽  
Bacterial Endotoxin ◽  
Tissue Explants ◽  
Gestational Tissues ◽  
Term Labour ◽  
Labour Onset

Abstract The aims of this study were to investigate the concentration and release of interleukin-1α (IL-1α) at the time of human term labour, and to study the regulation of IL-1α release from human gestational tissue explants by bacterial endotoxin. Immunoreactive IL-1α concentrations in maternal plasma, amniotic fluid and conditioned media from human amniotic, choriodecidual and placental explants were quantified before and after spontaneous term labour-onset and delivery. Furthermore, the effects of a bacterial endotoxin, lipopolysaccharide (LPS), on the release of IL-1α from human gestational tissue explants over a time course of 24 h (n=3) and LPS concentrations ranging from 10–107 pg/ml (n=3) were investigated. IL-1α concentrations in maternal plasma and amniotic fluid did not change significantly with spontaneous term labour-onset. In contrast, IL-1α was released in detectable amounts from human amniotic and choriodecidual explants only in association with term labour-onset and delivery. Similarly, placental release of IL-1α was increased significantly in explant cultures in association with term labour-onset and delivery. LPS increased IL-1α release significantly only from human placental explants from both term not-in-labour and term after-labour tissues. The data demonstrate differential regulation of IL-1α release from human gestational tissues in association with labour and LPS treatment and the observations support the hypothesis that the labour-associated increase in IL-1α release from the fetal membranes is independent of exposure to bacterial endotoxin. Journal of Endocrinology (1996) 150, 515–522

scholarly journals Quercetin Is a Flavonoid Breast Cancer Resistance Protein Inhibitor with an Impact on the Oral Pharmacokinetics of Sulfasalazine in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 397
Author(s):  
Yoo-Kyung Song ◽  
Jin-Ha Yoon ◽  
Jong Kyu Woo ◽  
Ju-Hee Kang ◽  
Kyeong-Ryoon Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cancer Resistance ◽  
Concentration Dependent Manner ◽  
Resistance Protein

The potential inhibitory effect of quercetin, a major plant flavonol, on breast cancer resistance protein (BCRP) activity was investigated in this study. The presence of quercetin significantly increased the cellular accumulation and associated cytotoxicity of the BCRP substrate mitoxantrone in human cervical cancer cells (HeLa cells) in a concentration-dependent manner. The transcellular efflux of prazosin, a stereotypical BCRP substrate, was also significantly reduced in the presence of quercetin in a bidirectional transport assay using human BCRP-overexpressing cells; further kinetic analysis revealed IC50 and Ki values of 4.22 and 3.91 μM, respectively. Moreover, pretreatment with 10 mg/kg quercetin in rats led to a 1.8-fold and 1.5-fold increase in the AUC8h (i.e., 44.5 ± 11.8 min∙μg/mL vs. 25.7 ± 9.98 min∙μg/mL, p < 0.05) and Cmax (i.e., 179 ± 23.0 ng/mL vs. 122 ± 23.2 ng/mL, p < 0.05) of orally administered sulfasalazine, respectively. Collectively, these results provide evidence that quercetin acts as an in vivo as well as in vitro inhibitor of BCRP. Considering the high dietary intake of quercetin as well as its consumption as a dietary supplement, issuing a caution regarding its food–drug interactions should be considered.

scholarly journals Interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin production by human osteoblastic cells: comparison of the effects of 17-beta oestradiol and raloxifene

2003 ◽  
Vol 177 (3) ◽  
pp. 423-433 ◽  
Author(s):  
J Cheung ◽  
YT Mak ◽  
S Papaioannou ◽  
BA Evans ◽  
I Fogelman ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
In Vivo Studies ◽  
Pcr Analysis ◽  
Nuclear Factor Kappab ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Treatment Change ◽  
Rankl Mrna ◽  
Receptor Activator

Oestrogen inhibits bone resorption, at least in part, by regulating the production of several cytokines, including interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) by cells of the osteoblastic lineage. The selective oestrogen receptor modulator raloxifene (RAL) acts on bone in a similar manner to oestrogen, although the mechanisms of action of RAL on osteoblasts still remain unclear. We investigated and compared the effects of 17-beta oestradiol (E(2)) and RAL on the regulation of IL-6, IL-1, RANKL and OPG in vitro in primary human osteoblastic (HOB) cells and in an immortalised clonal human bone marrow stromal cell line (HCC1) with osteoblastic characteristics. We tested E(2) and RAL at concentrations ranging from 10(-12) to 10(-6) M. IL-6, IL-1alpha and IL-1beta, OPG and RANKL were measured by ELISA. RANKL and OPG mRNA steady state level was assessed by quantitative PCR analysis. Both E(2) and RAL led to a significant reduction in IL-6 production in the HOB cells, although the effect was more marked with E(2) (P<0.05). IL-1alpha and IL-1beta also decreased significantly following treatment with E(2) and RAL in the HCC1 cells (E(2) (10(-8), 10(-7) and 10(-6) M), % reduction (means+/-S.E.M.) compared with vehicle-treated cells - IL-1alpha: 84+/-7.4, 70.8+/-2.9*, 78.2+/-4.8*; IL-1beta: 79+/-10, 72.8+/-8.2*, 66.6+/-2.8*; RAL (10(-8), 10(-7) and 10(-6) M) - IL-1alpha: 72.4+/-5*, 79+/- 5.2*, 102+/-7.7; IL-1beta: 67.9+/-3.2*, 69+/-2.5*, 73.8+/- 6.2*; *P<0.05). OPG protein concentration decreased significantly in a dose-dependent manner following treatment with E(2) and RAL (% reduction E(2) (10(-8), 10(-7) and 10(-6) M) - HOB: 72.5+/-8.4*, 80+/-6.7*, 62.8+/-8.9*; HCC1: 109+/-4, 98.8+/-6, 54.5+/-3.4*; RAL (10(-8), 10(-7) and 10(-6) M) - HOB: 81.5+/-5.5*, 62.7+/-7.4*, 55.2+/-10.9*; HCC1: 92.7+/-7.4, 67+/-12.2*, 39+/-4.5*; *P<0.05). In the HCC1 cells, RANKL protein did not change significantly following E(2). In contrast, a significant reduction in RANKL was seen with RAL at 10(-7) and 10(-6) M (66+/-6.4% and 74+/-3% respectively). There was no change in OPG mRNA expression following E(2) or RAL in the HCC1 cells, although in the HOB cells we observed a significant reduction in OPG mRNA. RANKL mRNA decreased significantly in the HCC1 cells following RAL (10(-8), 10(-7)and 10(-6) M) treatment (% change from controls: 52+/-2*, 62+/-1*, 53+/-5.8*; *P<0.05). Similar results were seen in the HOB cells with RAL at 10(-6) M (RANKL mRNA: 72+/-5.5, P<0.05). In addition, there was a significant decrease in the RANKL/OPG ratio after RAL at 10(-6) M (HOB: 65.6+/-5*, HCC1: 56.9+/-20*; *P<0.05). RANKL/OPG ratio did not change significantly in the HCC1 cells following E(2). However, in contrast to RAL, we observed an increase in the RANKL/OPG ratio in the HOB cells following treatment with E(2). In conclusion, the study shows that RAL and E(2) have divergent cell-specific effects on the regulation of cytokines. The data also suggest that, in contrast to E(2), RAL may exert its anti-resorptive actions, at least in part, via the RANKL/OPG pathway. Further in vivo studies are required to confirm this.

Hemostatic Properties of Infusible Trehalose-Stabilized Lyophilized Platelet Derivatives.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 834-834
Author(s):  
Keith A. Moskowitz ◽  
Josh Dee ◽  
Jason Barnidge ◽  
Ruth Sum ◽  
David Ho ◽  
...  
Keyword(s):  
Fluid Phase ◽  
Fold Increase ◽  
Submicron Particles ◽  
Cell Counting ◽  
Attractive Alternative ◽  
Dependent Manner ◽  
Clot Retraction ◽  
Drug Induced ◽  
Dose Dependent

Abstract Availability of platelet concentrates for treatment of bleeding associated with thrombocytopenia, trauma, or drug-induced coagulopathies is problematic due to the short 5 day platelet storage time and because platelets require controlled shaking at ambient temperature in order to remain viable, a condition which augments bacterial growth. To address the platelet availability problem we expanded upon trehalose cryo-preservation technology to create a lyophilized hemostatic platelet derivative. Washed platelets were stabilized by accumulation of 5–10 mM intracellular trehalose via fluid phase endocytosis then formulated with excipients and lyophilized. Lyophilized platelets were instantaneously rehydrated with > 90% recovery and were stable for at least 3–6 months at ambient temperatures. Rehydrated (RH) platelets responded quantitatively to α-and γ-thrombin and ristocetin by transmittance aggregometry and were partially agglutinated by collagen as judged by aggregometry and single cell counting using the Platelet Works® system. RH platelets co-aggregated in a dose dependent manner when mixed with fresh autologous platelets during collagen-induced activation. Aggregation response to low-dose thrombin and collagen was inhibited by the GPIIb/IIIa antagonist RGDS and by EGTA. RH platelets were quantitatively incorporated into fibrin clots and elicited platelet-dependent fibrin-clot retraction ~ 60% as well as fresh platelets. RH platelets were similar in size to fresh and had less than 25% submicron particles as judged by electronic particle counting and flow cytometry scatter profiles. RH platelets were partially activated upon rehydration as judged by anti P-selectin and anti-LAMP-3 binding, yet GPIIb/IIIa remained in a resting conformation, as judged by a lack of PAC-1 binding. GPIIb/IIIa receptors were present as judged by the binding of complex-dependent (clone 5B12) and function-blocking (clone P2) antibodies. RH platelets also contained intact GPIbα as judged by binding of the function-blocking MoAb AN51. Function of GPIIb/IIIa and collagen receptors on RH platelets was further demonstrated as RH platelets adhered to immobilized fibrinogen and collagen in the absence of added agonists and in a dose-dependent manner. Moreover, RH platelets exhibited a two-fold increase in platelet procoagulant activity in the presence of thrombin receptor agonist peptide SFLLRN as judged by Annexin-V binding. Procoagulant and hemostatic activity was further demonstrated as RH platelets accelerated the clotting of recalcified whole thrombocytopenic blood in a dose-dependent manner similarly to fresh platelets. Lastly, RH platelets corrected the coagulopathy induced by contact pathway inhibition with aprotinin during the recalcification of citrated whole blood. The technology has been scaled to single donor platelet aphaeresis units, equivalent to a standard transfusion dose. Preclinical animal models of safety, efficacy, and circulation persistence are currently being evaluated. In summary, trehalose- stabilized lyophilized platelet derivatives contain numerous in vitro hemostatic properties and may offer an attractive alternative to fresh platelet transfusions when the latter are indicated yet unavailable.

scholarly journals Stimulation of cell proliferation in skeletal tissues of the rat by defined parathyroid hormone fragments

1991 ◽  
Vol 277 (3) ◽  
pp. 863-868 ◽  
Author(s):  
D Sömjen ◽  
K D Schlüter ◽  
E Wingender ◽  
H Mayer ◽  
A M Kaye
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Thymidine Incorporation ◽  
Specific Activity ◽  
Fold Increase ◽  
Dependent Manner ◽  
Equimolar Concentration ◽  
Dose Dependent

We have found, in previous studies in vitro using skeletal derived cell cultures, that mid-region fragments of human parathyroid hormone (hPTH) stimulate [3H]thymidine incorporation into DNA and increase the specific activity of the brain-type isoenzyme of creatine kinase (CK). These changes occurred without an increase in cyclic AMP formation which is linked to bone resorption. In this study, we found that the mid-region fragment hPTH-(28-48) stimulated CK activity in diaphysis, epiphysis and kidney in a time- and dose-dependent manner, parallel to the effects of the whole molecule bovine (b)PTH-(1-84) and the fully active fragment hPTH-(1-34). The increase caused by hPTH-(28-48) at a dose of 1.25 micrograms/rat was not less than the 2-fold increase caused by a roughly equimolar concentration bPTH-(1-84). A significant increase was reached at 1 h after intraperitoneal injection in all cases. All three sequences of PTH caused an increase in [3H]thymidine incorporation into DNA in diaphysis and epiphysis, but not in kidney, 24 h after injection. A fragment further towards the C-terminal, hPTH-(34-47), was inactive compared with an equimolar concentration of the fragment hPTH-(25-39), which stimulated both CK activity and DNA synthesis. These results in vivo are in line with previous findings in vitro; they provide further support for the suggestion that mid-region fragments of the PTH molecule could be used to induce bone formation without incurring the deleterious effect of bone resorption.

scholarly journals A conformation-specific ON-switch for controlling CAR T cells with an orally available drug

2020 ◽  
Vol 117 (26) ◽  
pp. 14926-14935 ◽  
Author(s):  
Charlotte U. Zajc ◽  
Markus Dobersberger ◽  
Irene Schaffner ◽  
Georg Mlynek ◽  
Dominic Pühringer ◽  
...  
Keyword(s):  
T Cells ◽  
Small Molecule ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Fold Increase ◽  
Retinol Binding Protein ◽  
Dependent Manner ◽  
Car T Cells ◽  
Car T

Molecular ON-switches in which a chemical compound induces protein–protein interactions can allow cellular function to be controlled with small molecules. ON-switches based on clinically applicable compounds and human proteins would greatly facilitate their therapeutic use. Here, we developed an ON-switch system in which the human retinol binding protein 4 (hRBP4) of the lipocalin family interacts with engineered hRBP4 binders in a small molecule-dependent manner. Two different protein scaffolds were engineered to bind to hRBP4 when loaded with the orally available small molecule A1120. The crystal structure of an assembled ON-switch shows that the engineered binder specifically recognizes the conformational changes induced by A1120 in two loop regions of hRBP4. We demonstrate that this conformation-specific ON-switch is highly dependent on the presence of A1120, as demonstrated by an ∼500-fold increase in affinity upon addition of the small molecule drug. Furthermore, the ON-switch successfully regulated the activity of primary human CAR T cells in vitro. We anticipate that lipocalin-based ON-switches have the potential to be broadly applied for the safe pharmacological control of cellular therapeutics.

scholarly journals Preparation and Characterization of Callus Extract from Pyrus pyrifolia and Investigation of Its Effects on Skin Regeneration

Cosmetics ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 71 ◽  
Author(s):  
Dae Park ◽  
Deepak Adhikari ◽  
Rudra Pangeni ◽  
Vijay Panthi ◽  
Hyun Kim ◽  
...  
Keyword(s):  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Fold Increase ◽  
Fibroblast Cell ◽  
Product Formation ◽  
Pyrus Pyrifolia ◽  
Type I ◽  
Dependent Manner ◽  
Procollagen Type

In the present study, an aqueous extract was prepared using calli from the in vitro-derived leaves of Pyrus pyrifolia cultured in Murashige and Skoog medium containing picloram for a plant growth regulator. The major biological components in the callus extract were identified as uridine (1), adenosine (2), and guanosine (3). In terms of the antioxidant activity, at 300 µg/mL, the extract exhibited free radical scavenging activity of 76.9% ± 2.88% in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, comparable to that of 44 µg/mL ascorbic acid (82.5% ± 3.63%). In addition, the IC50 values for inhibition of advanced glycation end product formation from collagen and elastin were 602 ± 2.72 and 3037 ± 102.5 µg/mL, respectively. The extract significantly promoted keratinocyte and fibroblast cell proliferation in a dose-dependent manner. Moreover, fibroblasts treated with 1.36 µg/mL extract exhibited a 1.60-fold increase in procollagen type I C-peptide level compared to controls. The in vitro wound recovery rates of keratinocytes and fibroblasts were also 75% and 38% greater, respectively, than those of serum-free controls at 9 and 36 h after extract treatment (1.36 µg/mL). Additionally, the extract flux across the human epidermis increased by 1598% after its incorporation into elastic nanoliposomes (NLs). Therefore, elastic NLs loaded with Pyrus pyrifolia callus extract have potential use as skin rejuvenators and antiaging ingredients in cosmetic formulations.

A long-lasting, plasmin-activatable thrombin inhibitor aids clot lysis in vitro and does not promote bleeding in vivo

2009 ◽  
Vol 101 (05) ◽  
pp. 867-877 ◽  
Author(s):  
Louise Eltringham-Smith ◽  
Sharon Gataiance ◽  
Varsha Bhakta ◽  
William Sheffield
Keyword(s):  
Chimeric Protein ◽  
Fold Increase ◽  
Thrombin Inhibitor ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Recombinant Hirudin ◽  
Concentration Dependent Manner ◽  
Shed Blood

SummaryThe leech protein hirudin is a potent inhibitor of thrombin, but clinical use of recombinant hirudin is restricted by haemorrhagic risks, and complicated by hirudin’s rapid clearance from the circulation. We previously employed albumin fusion to slow hirudin variant 3 (HV3) clearance. In this study, we hypothesized that reconfiguration of the chimera, appending human serum albumin (HSA) to the N-terminus of HV3, with an intervening plasmin cleavage site, would create a slowly cleared, plasmin-activatable HV3. Potential plasmin cleavage sites were screened by expression in Escherichia coli, interposed between glutathione sulfotransferase and HV3 domains. The most reactive sequence (GSGIYR-ITY) was recreated in C-terminally His-tagged albumin fusion protein HSACHV3, expressed in Pichia pastoris yeast and purified by nickel-chelate affinity chromatography. HSACHV3 showed no thrombin inhibitory activity in the absence of plasmin, but liberated active HV3 in a time- and concentration-dependent manner in its presence. In a discontinuous clot assay involving clot-bound thrombin, HSACHV3 assisted clot lysis by limiting clot extension in a tPA- and concentration-dependent manner. Similar results were obtained in plasma at higher concentrations of HSACHV3. The chimeric protein exhibited much slower clearance in mice than unfused HV3, and indistinguishable pharmacokinetics from unfused recombinant HSA. In a mouse tail transection bleeding model, doses of HSACHV3 identical to those of HV3 that elicited a four-fold increase in the volume of shed blood were without effect. Our results suggest that HSACHV3 is a fully latent, plasmin activatable, long-lasting hirudin, of potential benefit in thrombotic disorders resistant to natural or pharmacological clot lysis.

scholarly journals Localisation and temporal changes in prostaglandin G/H synthase-1 and -2 content in ovine intrauterine tissues in relation to glucocorticoid-induced and spontaneous labour

2000 ◽  
Vol 165 (2) ◽  
pp. 399-410 ◽  
Author(s):  
WJ McLaren ◽  
IR Young ◽  
GE Rice
Keyword(s):  
Time Course ◽  
Polyclonal Antibodies ◽  
Placental Tissue ◽  
Fold Increase ◽  
Fetal Membranes ◽  
Western Blots ◽  
Protein Levels ◽  
Tissue Extracts ◽  
Term Labour ◽  
Labour Onset

Parturition in the ewe is preceded by an increase in the synthesis of prostaglandins (PGs) by gestational tissues. To establish the uterine source of these PGs, placental cotyledons, fetal membranes and maternal uterine tissues were collected from ewes (n=6) at spontaneous parturition. Solubilised tissue extracts were prepared and analysed by Western blots using polyclonal antibodies to PG G/H synthase-1 and -2 (PGHS-1 and PGHS-2). PGHS-1 was expressed by all intrauterine tissues at term labour. Densitometric analysis of Western blot autoradiographs showed that the fetal membranes and maternal cervix contained the largest amounts of PGHS-1. PGHS-1 enzyme content of ovine amnion was significantly greater than that of either chorion or allantois (P<0.05). PGHS-1 protein content of myometrial, endometrial and cotyledonary tissue extracts was minimal. Formation of the PGHS-2 isozyme was confined to placental tissue at term labour. PGHS-2 protein levels in sheep placenta were significantly higher than those of PGHS-1 in all intrauterine tissues examined. This result supports the hypothesis that PGHS-2 is a major contributor to PG formation at term labour. To elucidate the developmental changes in PGHS-1 and PGHS-2 relative to labour onset, an experimental paradigm of glucocorticoid-induced delivery was used. Previous characterisation and validation of this labour model demonstrated that direct, transabdominal, intrafetal injection of the synthetic glucocorticoid betamethasone (5.7 mg in 1 ml aqueous vehicle) on day 131 of gestation induced labour onset in 56.6+/-0.8 h (mean+/-s.e.m.). As the latent period to induced-labour was known, the time course of enzyme formation could be ascertained. Sheep (n=20) were killed by barbiturate injection at various time intervals post-injection (0, 14, 28, 42 and 56 h). Tissue extracts collected at post-mortem examination were prepared and analysed by Western blots. PGHS-2 was induced in ovine cotyledon in a time-dependent fashion following glucocorticoid injection (P<0.05). There was a 12-fold increase in abundance between the time of betamethasone administration (0 h) and established labour (56 h). The PGHS-2 isozyme was not detected in any of the other tissues examined. In contrast, formation of the PGHS-1 isozyme did not change in relation to induced-labour in any of the intrauterine tissues. This finding is consistent with constitutive formation of PGHS-1. Previous studies have demonstrated a rise in PG production in association with glucocorticoid-induced labour and spontaneous delivery. The results of the present study indicate that this rise in PG production is due to increased formation of the PGHS-2 isozyme in ovine cotyledon. PGHS-2 appears to be induced by exogenous glucocorticoid administration and/or the mechanisms controlling ovine parturition. The role of PG formation by the fetal membranes is yet to be elucidated.

Measurement of interleukin-1 alpha and interleukin-6 in pregnancy-associated tissues

1996 ◽  
Vol 8 (7) ◽  
pp. 1069 ◽  
Author(s):  
L Gunn ◽  
P Hardiman ◽  
S Tharmaratnam ◽  
D Lowe ◽  
T Chard
Keyword(s):  
Amniotic Fluid ◽  
Interleukin 1 ◽  
Elective Caesarean Section ◽  
Maternal Blood ◽  
Fetal Membranes ◽  
Fetal Blood ◽  
Tissue Extracts ◽  
Arterial Blood ◽  
Term Labour ◽  
In Pregnancy

The concentrations of interleukin-1 alpha (IL-1 alpha) and IL-6 in pregnancy-associated tissues were investigated in term labour and delivery in the absence of labour (elective Caesarean section). Samples of amniotic fluid, placenta, fetal membranes, umbilical venous and, where possible, umbilical arterial blood were collected at delivery (37-41 weeks of gestation). Maternal blood was sampled during labour. Fluid and tissue extracts were assayed for IL-1 alpha and IL-6 by radioimmunoassay. Placenta and membranes were examined histologically for evidence of infection. Concentrations of IL-1 alpha and IL-6 in amniotic fluid and membrane extract, and IL-1 alpha in maternal and fetal blood, were raised after the onset of labour. Concentrations of both cytokines in the placenta remained unchanged. There was a good correlation between concentrations of both cytokines in amniotic fluid and membranes. There was also a significant correlation between concentrations of IL-1 alpha and IL-6 in amniotic fluid, placenta and membranes. It is suggested that the fetal membranes or maternal decidua, but not the placenta, internal fetal or maternal tissues, are the main sources of IL-1 alpha and IL-6 during labour.

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