IL-1beta, IL-6 and IL-8 levels in gyneco-obstetric infections

OBJECTIVE: During pregnancy cytokines and inflammatory mediators stimulate the expression of prostaglandin, the levels of which determine the onset of labor. The aim of this work was to study interleukin IL-1beta, IL-6 and IL-8 levels in the vaginal discharge, serum and urine of pregnant women with genitourinary infection before and after specific treatment. One hundred and fifty-one patients were studied during the second or third trimester of their pregnancy. METHODS: The selected patients were: healthy or control group (n = 52), those with bacterial vaginosis (n = 47), those with vaginitis (n = 37), those with asymptomatic urinary infection (n = 15) and post-treatment. The level of cytokines was assayed by ELISA test. The Mann-Whitney U-test was used for statistical analysis. RESULTS: The IL-1beta levels in vaginal discharge were: control 103.5 +/- 24.2 pg/ml, bacterial vaginosis 1030 +/- 59.5, vaginitis 749.14 +/- 66.7l ( p < 0.0001), post-treatment 101.4 +/- 28.7. IL-6 values were similar in both control and infected groups, and there were no patients with chorioamnionitis. In vaginal discharge IL-6: control 14.2 +/- 3.9 pg/ml, bacterial vaginosis 13.2 +/- 3.8, vaginitis 13 +/- 4.2. IL-8 levels were: control 1643 +/- 130.3 pg/ml, bacterial vaginosis 2612.7 +/- 257.7, vaginitis 3437 +/- 460 (p < 0.0001), post-treatment 1693 +/- 126.6. In urine the results were: control 40.2 +/- 17 pg/ml, asymptomatic urinary infection 1200.7 +/- 375 (p < 0.0001). In patients with therapeutic success both IL-1beta and IL-8 returned to normal levels. CONCLUSIONS: Genitourinary infections induce a significant increase in IL-1beta and IL-8 levels in vaginal secretions, and IL-8 in urine as well. Both cytokines could be useful as evolutive markers of infection.     

Chemokines in the diagnosis of neonatal infections

Bacterial infection is a major cause of neonatal morbidity and mortality. The increased susceptibility of the neonate especially premature one, for bacterial infection is the result of several factors including a delayed maturation of immune response of neonatal B and T cells and deficiencies of the myelopoetic system. Chemokines constitute a large family of chemotactic cytokines with proinflammatory action, which are produced by large variety of cells. Although most inflammatory chemoatractants are only induced and released in the circulation during acute infection Large epidemiology studies are needed to clarify relationships among inflammation markers and their expression in the fetal and neonatal circulation over time. Such studies would also add to our understanding of the possible role of chemokines in the pathophysiology of the major complications of the neonate, especially premature one.     

Evaluation of congenital infection risk on the basic of cytokines Il-1 beta,Il-6 and TNF alpha levels in blood serum and amniotic liquid in pregnant women and in umbilical blood of neonates

OBJECTIVE: The aim of the study was to evaluate congenital infection risk on the basic of cytokines IL-1 beta, IL-6 and TNF alpha levels in blood serum and amniotic liquid in pregnant women and in umbilical blood of neonates. MATERIALS AND METHODS: The study was carried out on 37 women in labor including 17 mothers with normal pregnancy (group A-test) and 20 suspected of intrauterine infection (group C). There have been indicated cytokines IL-1 beta, IL-6 and TNF alpha in amniotic liquid and in blood serum collected in the second stage of labor and in umbilical blood serum. The accepted procedure used in our study resulted from the assumption that the analysis of cytokines in amniotic liquid collected without amniocentesis was beneficial. RESULTS: It has been proved that among women in labor from group C there is a high concentration of IL-6 and TNF alpha in amniotic liquid that has statistic significance as far as markers for women with normal pregnancy are concerned (group A). Lower levels of IL-6 than in amniotic liquid but statistically meaningful in relation to the markers in group A have been detected in serum collected from pregnant women and in the umbilical blood of the neonates. Among 18 neonates delivered by mothers from group C the symptoms of congenital infection have appeared. CONCLUSION: Extending diagnostics of congenital infection on the basis of the analyzed cytokines, mainly IL-6 in the second stage of labor, is of prognostic significance.     

A Case of Cervical Cancer with Aggressive Tumor Growth: Possible Autocrine Growth Stimulation by G-CSF and Il-6

Background. Patients with tumors that produce hematopoietic growth factors, such as G-CSF, sometimes exhibit leukemoid reactions. Squamous cell carcinomas of the uterine cervix producing such factors are rarely reported.Case. A 56-year-old woman had severe leukocytosis (>50 × 10³/μl) and fever without evidence of infection after radical hysterectomy for treatment of her cervical cancer. The parametrial recurrent mass appeared after the operation and exhibited extremely aggressive growth. Serum levels of G-CSF and IL-6 were extremely high, and immunohistochemical analysis and RT-PCR assays revealed that G-CSF and IL-6 as well as their receptors were produced in tumor cells.Conclusions. This is a case of cervical cancer which exhibited an aggressive clinical course, possibly due to autocrine stimulation of cell growth by G-CSF and IL-6.     

Maternal serum interleukin-1 beta, -6 and -8 levels and potential determinants in pregnancy and peripartum

AIMS: To measure maternal serum interleukins (IL) in pregnancy, delivery and early puerperium, and to identify their potential determinants. METHODS: Prospective longitudinal measures of serum IL-1 beta, IL-6 and IL-8 in 38 healthy pregnant women at antenatal visits, through labor and delivery, with clinical correlates (infection, vaginal hemorrhage and anemia) recorded by questionnaire. RESULTS: Pregnancy IL levels remained consistently low. IL-1 beta increased shortly before delivery, then returned to pregnant levels, except where blood loss exceeded 500 ml. IL-6 and IL-8 rose at labor onset and exceeded pregnancy levels through postpartum day three. Postpartum IL-6 was higher after non-elective cesarean section than after spontaneous delivery (P < 0.0001), and where blood loss exceeded 500 ml. IL-6 and IL-8 were higher with systemic infection during delivery (P < 0.0001) and on postpartum day one (P < 0.05); IL-8 was higher in anemia (delivery: P < 0.005; postpartum day 1: P < 0.05). Differences due to delivery mode and systemic infection remained significant after correction for other conditions. CONCLUSIONS: Labor-dependent inflammation increases all IL levels at delivery. Further studies with larger sample sizes are required to establish reference values differentiating physiology from pathology as an aid to peripartum management.     

Soluble intercellular adhesion molecule 1 in umbilical cord serum: potential for the diagnosis of neonatal infections

OBJECTIVE: To evaluate the diagnostic relevance to neonatal infections of the soluble intercellular adhesion molecule 1 (sICAM-1) cord serum level. METHODS: The case-control study included 66 term newborn infants with and without risk factors for neonatal infections. Cord blood serum determinations of white blood cell count, C-reactive protein, fibrinogen, and sICAM-1 were systematically performed associated with bacterial cultures from placenta, ears, and gastric fluids. RESULTS: 6 of 33 infants (18.2%) with risk factors were infected, and 13 (39.4%) were colonized. Two infants included in the group without infection risk factors (n = 33) were colonized. No difference in sICAM-1 cord serum levels was found according to the presence of premature rupture of membrane, fetal tachycardia >160 bpm, meconial amniotic fluid, and duration of labour >10 h. No difference in sICAM-1 was noted between infected and non-infected infants. The cord serum levels of sICAM-1 were significantly higher in infants after forceps extraction (p = 0.01). A correlation was observed between sICAM-1 and C-reactive protein cord serum levels (p = 0.004, r = 0.371) and between sICAM-1 level and neutrophil count (p = 0.01, r = 0.489). CONCLUSIONS: Our results suggest that cord serum sICAM-1 determinations have no diagnostic relevance to neonatal infection. The increase of sICAM-1 cord serum levels in infants after forceps extraction suggests its potential to evaluate cerebral trauma or hypoxia.     

The value of interleukin-8, interleukin-6 and interleukin-1beta in vaginal wash as predictors of preterm delivery

AIMS: To study the value of interleukin (IL)-8, IL-6 and IL-1beta in vaginal wash as predictors of preterm delivery. METHODS: A prospective analysis of a study group of 200 pregnant women between 24 and 34 weeks of gestation with intact membranes and preterm labor and a control group of 50 pregnant women during the same period of gestation. The controls had uncomplicated pregnancies and subsequently delivered at term. Samples of vaginal secretions were collected from both groups and analyzed for IL-1beta, IL-6 and IL-8 concentrations. RESULTS: Of the women in the study group, 70 had preterm deliveries, while all women in the control group had full-term deliveries. Compared with the control group, the study group had significantly higher concentrations (p < 0.021) of IL-1beta, IL-6 and IL-8. The women in the study group delivering preterm also had IL-1beta, IL-6 and IL-8 concentrations significantly greater (p < 0.001) than those of the same group delivering full term. ROC curves were used to establish cut-off points for the three interleukins to predict preterm delivery. We did not find a cut-off point with an appropriate sensitivity and specificity. CONCLUSION: The concentrations of interleukins in vaginal wash were significantly higher both in the women with preterm labor and in those delivering preterm. While values differed between controls and those with the preterm labor, no cut-off can be obtained to use the results of IL-1beta, IL-6 and IL-8 as a predictor clinically.     

Maternal serum and amniotic fluid IL-1 alpha, IL-1 beta, IL-6 and IL-8 levels in preterm and term labor complicated by PROM

Cytokines may be implicated in the pathophysiologic mechanisms of preterm and term labor. Many studies indicate cytokines as predictors of preterm delivery and explain partially mechanism of preterm uterine contractions. Complicated relations between mediators in systemic fluids of a fetomaternal unit require further explorations. The right diagnosis and management require better understanding of these relationships. OBJECTIVES: The comparison of IL-1 alpha, IL-1 beta, IL-6 and IL-8 levels in maternal serum and amniotic fluid in term and preterm labor complicated by PROM. MATERIAL AND METHODS: In 44 patients in premature labor with PROM (group I) and 33 patients in labor at term with PROM (group II) cytokines levels were estimated one time in amniotic fluid: just after PROM, and two times in maternal serum: just after PROM and during labor. RESULTS: Amniotic fluid cytokines levels were significantly higher in group I than in group II. Maternal serum cytokines concentrations of IL-1 alpha and IL-1 beta in group I were significantly higher than in group II. IL-6 level was significantly higher in group II than in group I. In both groups maternal serum IL-6 levels during labor significantly increased in comparison to IL-6 levels just after PROM. No correlations between amniotic fluid and maternal serum cytokine levels at PROM were observed. CONCLUSIONS: Higher amniotic fluid cytokines levels in patients with preterm labor complicated by PROM than in labor at term with PROM indicate possible differences between PROM mechanisms in preterm and term labor. The increase of IL-6 level during labor can be related with the possible role of this cytokine in the immunological mechanism of the labor beginning. No relationships between amniotic fluid and maternal serum levels of investigated cytokines in PROM suggest the presence of the barrier stopped cytokines transfer by the placenta and the complete separation of these two compartments.     

Maternal plasma interleukin-6, interleukin-1beta and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery.

OBJECTIVE: To investigate whether maternal serum interleukin-6 (IL-6), interleukin-1beta (IL-1beta) and high sensitive C-reactive protein (CRP) could be used as markers of tocolysis failure and adverse neonatal outcome in pregnancies with preterm labor (PL). METHODS: Forty-seven maternal blood samples taken because of PL at admission and delivery were analyzed. Control samples were taken from 20 gravidas with normal pregnancies. Differences in interleukins and CRP levels with or without chorioamnionitis, connatal infection or periventricular leukomalacia (PVL) were analyzed. Cut-off values were estimated for prediction of tocolysis failure and adverse neonatal outcome. RESULTS: All three parameters were significantly higher in patients delivering prematurely than in patients delivering at term. All three parameters were significantly higher with than without histologic chorioamnionitis (p < 0.001), with than without connatal infection (p < 0.01), with than without PVL (p < 0.01 for IL-6 and IL-1beta, p < 0.05 for CRP), and in pregnancies with preterm premature rupture of membranes (PPROM) delivered within 48 hours compared to those more prolonged (p < 0.01). Choosing 50.9 pg/mL of IL-6 and a CRP of 19.7 as cut-offs in maternal blood admission concentrations for neonatal PVL, resulted in sensitivity of 81% and specificity of 91% and sensitivity of 91% and specificity of 81%, respectively. At respective maternal blood admission cut-off levels of 27.8 pg/mL of IL-6 and 8.9 of CRP, both parameters were effective predictors of connatal infection. CONCLUSIONS: Maternal blood IL-6 and CRP could become useful in predicting tocolysis failure and intrauterine treat for the fetus.     

Amniotic fluid concentrations of interleukin-1beta, interleukin-6 and TNF-alpha in chorioamnionitis before 32 weeks of gestation: histological associations and neonatal outcome.

OBJECTIVES: To test the association between cytokine levels in the amniotic fluid and (i) the vascular invasion phase of intrauterine infection, (ii) the occurrence of periventricular leukomalacia; to assess the correlation between C-reactive protein levels, a recognised biological marker of inflammation in maternal serum and cytokine levels in the amniotic fluid. DESIGN: Prospective clinical study. SETTING: Fetal medicine unit and neonatal intensive care unit, Antoine Beclere Hospital, Clamart, France. SAMPLE: Thirty-one pregnancies complicated by chorioamnionitis leading to birth before 32 weeks of gestation. METHODS: Interleukin 1-beta, Interleukin 6 and TNF-alpha prospectively measured in the amniotic fluid. Histological examination of the placenta. Ultrasound examination and magnetic resonance imaging of the brains of the newborn infants performed within the first week of life. MAIN OUTCOME MEASURES: The occurrence of periventricular leukomalacia was assessed by transfontanellar ultrasound and magnetic resonance imaging. RESULTS: There was a significant positive correlation between the occurrence of histological chorioamnionitis, vascular extension of infection of the membranes, maternal inflammatory syndrome and neonatal sepsis. A strong association was found between maternal serum C-reactive protein concentrations and cytokine levels in the amniotic fluid. Interleukin-1beta was the best predictor of vascular extension of chorioamnionitis, and TNF-alpha was the best predictor of the development of severe early neonatal infection. There was no association between the amniotic fluid levels of cytokines and the development of periventricular leukomalacia. CONCLUSIONS: These data suggest that IL-1beta, IL-6 and TNF-alpha are produced in relation to intrauterine inflammation and infection, but cannot be directly implicated in the development of fetal cerebral white matter lesions.     

Production of interleukins 1beta, 6 and 8 and tumor necrosis factor alpha in separated and cultured endometrial and endometriotic stromal and epithelial cells

The production of IL-1beta, IL-6, IL-8 and TNF-alpha was studied in short-time culture of separated stromal and epithelial cells. The cytokine secretion into culture medium was analyzed using immunoassay to evaluate the cytokine protein levels and bioassay to assess the bioactivity of the cytokines. Tissue samples of endometrium and ovarian endometriomas were obtained from 4 patients operated on for clinical reasons. Only IL-8 was found in all samples. IL-1beta and TNF-alpha were detected in the culture medium from most stromal cell samples, but in fewer media from epithelial cell samples. IL-6 was measurable in a few medium samples. Few of the samples displayed a bioactivity. There was no obvious difference between endometrium and endometriotic cell samples besides the production of IL-8 that seems to be lower in endometriotic tissue.     

Variability of influenza AH1N1 infections in a neonatal unit in Spain

We describe three positive influenza AH1N1 cases in a neonatal unit during the influenza pandemic in Spain. One term baby presented with an upper respiratory tract infection, another preterm infant with an apnea episode following nosocomial infection, and thirdly, a term infant of a mother with influenza AH1N1 had severe respiratory distress and pneumothoraces needing high-frequency ventilation.     

Interleukin 1beta, interleukin-6, and tumor necrosis factor-alpha in endometriotic tissue and in endometrium

OBJECTIVE: To compare the levels of IL-1beta, IL-6, and TNFalpha in endometriotic tissue and in endometrium from women with endometriosis and healthy controls. DESIGN: Open. SETTING: Department of Obstetrics and Gynecology at a university hospital. PATIENT(S): Twenty-six women with endometriosis and 22 controls operated on for clinical indications. INTERVENTION(S): ELISA in homogenized tissue samples collected during surgery. MAIN OUTCOME MEASURE(S): Levels of IL-1beta, IL-6, and TNFalpha in tissue homogenates. RESULT(S): The three types of tissue differed significantly with respect to all three cytokines. Endometriotic tissue had significantly higher concentrations of IL-1beta than endometrium from both patients with endometriosis and healthy controls. Both endometriotic tissue and endometrium from patients had significantly higher concentrations of IL-6, and endometriotic tissue had significantly lower concentration of TNFalpha than did endometrium from controls. IL-1beta showed a cycle phase dependence that was significant in endometrium from patients, being higher in the secretory than in the follicular phase. IL-1beta was significantly higher in endometrioma than in lesions of other localizations. Concentrations of IL-1beta and IL-6 were positively correlated in endometriotic tissue and in endometrium from controls. No other significant correlations were found. CONCLUSION(S): This study has shown a significant production of IL-1beta, IL-6, and TNFalpha in endometriotic tissue and endometrium, with significant differences between the tissue types, indicating a deviating cytokine pattern in both endometriotic tissue and endometrium from women with endometriosis compared with that from healthy controls.     

Antepartum use of antibiotics and early-onset neonatal sepsis: the next 4 years

OBJECTIVE: The purpose of this study was to analyze the incidence of early-onset neonatal sepsis and the presence of antibiotic resistance of the isolated bacteria and its relationship to antibiotic chemoprophylaxis that occurred during the 4 years that followed the publication of the most recent group B streptococcal guidelines. STUDY DESIGN: A prospective cohort study was performed between January 1, 1997, and December 31, 2000. All cases of early-onset neonatal sepsis were gathered prospectively. Data concerning the use of antepartum antibiotics, the isolated bacteria, and the presence of drug resistance were collected. These data were analyzed separately and were combined with published data from the preceding 6 years. RESULTS: A total of 26 cases of blood culture-proved early-onset neonatal sepsis occurred during the current 4-year study period. Group B Streptococcus was responsible for 10 cases, and the remaining 16 cases were non-group B streptococcal organisms. Of these 16 cases, 11 parturients received antibiotic chemoprophylaxis, and 10 of the isolates (91%) were resistant to the drug that was administered, compared with only one resistant bacteria (20%) in the 5 parturients who did not receive treatment (P =.01). In combining these 16 cases with the cases from the preceding 6 years, a total of 43 cases of non-group B streptococcal sepsis occurred in 49,788 deliveries. Of these, 26 mothers were given antepartum antibiotics, and 23 of the bacterial isolates (88%) exhibited resistance, compared with only 3 of the 17 cases (18%) in which antibiotics were not dispensed (P <.00001). However, because the overall use of antepartum antibiotics increased over time, the attack rate for early-onset group B Streptococcus significantly decreased by 75% (P <.000001). CONCLUSION: When early-onset neonatal sepsis develops in a case in which antepartum chemoprophylaxis was used, the bacterial isolate will most likely demonstrate resistance to the antibiotic that was administered. However, the development of early-onset group B streptococcal neonatal sepsis significantly decreased as the use of antepartum antibiotics increased. Thus, the number of prevented infections from antepartum antibiotic use may still outweigh the problems that are seen when resistant bacterial infections arise. Nevertheless, based on the current protocols, a large number of parturients are candidates for antibiotic chemoprophylaxis and this, in conjunction with the global concern of bacterial drug resistance, should be motivation to examine alternative methods, such as vaginal washing or immunotherapy, for decreasing infection.     

Liberal diagnosis and treatment of intrauterine infection reduces early-onset neonatal group B streptococcal infection but not sepsis by other pathogens

OBJECTIVE: Comparison of the incidence and case fatality of early-onset group B streptococcus sepsis and sepsis caused by other pathogens in neonates after change of management of intrauterine infection. METHODS: All infants delivered from 1988 through 1997 at a gestational age > or = 24 weeks with a birth weight > or = 500 gram without lethal congenital abnormalities were eligible for inclusion. Infants delivered by cesarean section before the onset of labor or rupture of membranes were excluded. During the first period (1988-1991) intrauterine infection was diagnosed by a temperature > 38 degrees C, during the second period (1992-1997) this diagnosis was made at a lower temperature (> or = 37.8 degrees C) or by fetal tachycardia > or = 160/min. Treatment of intrauterine infection was similar during both periods with 3 x 2 gram amoxicillin and 1 x 240 mg gentamicin every 24 hours intravenously during labor. Prophylactic treatment during labor was only given to women with a history of an earlier infant with early-onset group B streptococcus sepsis. RESULTS: During the first period 6,103 infants were included, during the second period 8,504. Intrauterine infection was diagnosed and treated more often in the second period (7.1% vs. 2.6%). The incidence of early-onset group B streptococcus sepsis was significantly lower in the second period than in the first period [0.2% vs. 0.4%; OR 0.5 (0.3-0.9)] and survival without disability higher [80% vs. 52%; OR 4.5 (1.4-16.5)]. However, in both periods the overall incidence of neonatal sepsis (3.6% vs. 3.5%) and overall mortality because of sepsis (14.3% vs.13.1%) were similar. CONCLUSIONS: Although the early detection of clinical signs of intrauterine infection might have been effective for the prevention of serious sequelae of early-onset group B streptococcus sepsis the overall incidence and mortality from neonatal sepsis remained unchanged. Evaluation of preventive measures for early-onset group B streptococcus sepsis should always take the incidence of neonatal sepsis caused by other pathogens into account.