Michelle Bates

Cytokine promoter gene polymorphisms and idiopathic recurrent pregnancy loss.

Approximately one in 300 women experience recurrent pregnancy loss (RPL), the aetiology of which is unknown in at least 40% of cases. Previously, some studies have shown increased production of pro-inflammatory cytokines (tumour necrosis factor-alpha and interferon-gamma) and reduced production of anti-inflammatory cytokines (interleukin-10) by circulating blood lymphocytes isolated from these patients when compared with controls. The reasons for this are unclear. The production of these cytokines are partly under genetic control. This study investigated whether polymorphisms in these three cytokine genes known to be associated with either high or low production, are associated with idiopathic RPL. No association was found. It may be that genetic factors are not a major determinant of cytokine production during pregnancy, or alternatively it may be that the observed differences in cytokine production by peripheral lymphocytes do not accurately indicate what is occurring at the local maternofoetal interface during successful and abortive pregnancies.

Does sustained lung inflation at resuscitation reduce lung injury in the preterm infant

Background: Bronchopulmonary dysplasia (BPD) is a common outcome of preterm birth. Experimental animal work has shown that initial ventilation strategies injure the immature lung and may lead to BPD. Studies with asphyxiated babies have shown that, if tidal ventilation at birth is preceded by sustained lung inflation, larger inflation volumes can be achieved, which is thought to lead to clearance of lung fluid and formation of the functional residual capacity (FRC). Objective: To see if sustained lung inflation at initial resuscitation of preterm babies would facilitate the removal of lung fluid, establish the FRC, and allow an even distribution of alveolar opening, permitting less aggressive ventilation, leading to a reduction in pulmonary inflammation and subsequent BPD. Method: The outcomes of 52 babies of less than 31 weeks gestation, resuscitated at birth using either a sustained lung inflation of five seconds or a conventional lung inflation of two seconds for the first assisted breath of resuscitation, were examined. Evidence of pulmonary inflammation was determined by quantification of interleukins 6, 10, and 1β and tumour necrosis factor α in bronchoalveolar lavage fluid by enzyme linked immunosorbent assay. Results: There were no significant differences in any of the cytokines. Death occurred in 3/26 babies in the conventional group and 6/26 babies in the sustained lung inflation group. Survival without BPD occurred in 13/26 and 14/26 respectively. Conclusion: The use of sustained lung inflation at resuscitation did not reduce lung injury, as measured by inflammatory markers.

Does the use of 50% oxygen at birth in preterm infants reduce lung injury?

Background: Bronchopulmonary dysplasia is an inflammatory fibrotic condition produced as a consequence of injurious influences in the neonatal lung. Exposing the premature lung to high concentrations of oxygen is thought to play an important part in lung injury pathogenesis. Objective: To see if the amount of oxygen used during resuscitation at birth triggers events that lead to the subsequent lung injury and if a reduction in oxygen used leads to a reduction in lung injury. Method: The outcomes of newborn babies less than 31 weeks gestation who were resuscitated using either 50% or 100% oxygen were examined. Eight of the babies receiving 50% oxygen required an increase in their oxygen concentration. Evidence of pulmonary inflammation was determined by quantifying interleukin 6, 1β, and 10 and tumour necrosis factor α in bronchoalveolar lavage fluid by enzyme linked immunosorbent assay. Results: There were no significant differences in any of the cytokines studied in either of the groups. Death occurred in 5/26 (19%) babies who received 100% oxygen and 4/26 (15%) babies who received 50% oxygen. Survival without bronchopulmonary dysplasia at 36 weeks postmenstrual age occurred in 14/26 (54%) and 13/26 (50%). Conclusion: Reducing the oxygen to 50% at resuscitation did not influence either short or long term outcomes, but a small benefit could not be excluded. There was no increase in adverse clinical outcomes in babies who received 100% oxygen.

Follicular fluid concentrations of interleukin-12 and interleukin-8 in IVF cycles

OBJECTIVE To investigate the role of interleukin-12 (IL-12) and IL-8 in the periovulatory follicular fluid during in vitro fertilization cycles. DESIGN A prospective study. SETTING Reproductive Medicine Unit, Liverpool Womens Hospital, United Kingdom. PATIENT(S) Women undergoing in vitro fertilization treatment. INTERVENTION(S) IL-8 and IL-12 concentrations in follicular fluid samples that had been collected during transvaginal oocyte retrieval were measured using an enzyme-linked immunosorbent assay (ELISA). Cytokine concentrations were correlated to fertilization rates and treatment outcome. MAIN OUTCOME MEASURE(S) Fertilization rates and ultrasonographic evidence of intrauterine pregnancy by 4 weeks after embryo transfer. RESULT(S) Failed fertilization in women with detectable IL-12 was significantly higher (45.5%) than in the IL-12 negative group (6.1%), P=.01. None of the women with detectable IL-12 achieved a pregnancy at the end of the treatment (P=.01). IL-8 was present in the follicular fluid of all women, and no difference in its concentrations was found between the pregnant and nonpregnant groups. No correlation was found between the follicular fluid concentrations of IL-8 and fertilization rates. CONCLUSION(S) The presence of IL-12 in the follicular fluid appears to be associated with a negative outcome in IVF treatment. Interleukin-8 appears to be an essential part of folliculogenesis, although its concentration is not associated with fertilization or implantation rates.

Leukocytes in semen from men with spinal cord injuries.

OBJECTIVE To assess the leukocyte populations in semen samples from men with spinal cord injuries (SCIs) and their relation to sperm motility. DESIGN Cross-sectional study. SETTING A joint spinal cord injury and fertility clinic at an academic tertiary referral center for fertility treatment and a university-based department of immunology. PATIENT(S) Nine men with chronic SCIs and seven healthy sperm donors as controls. INTERVENTION(S) Semen samples were obtained by electroejaculation from men with SCIs and by masturbation from donors. MAIN OUTCOME MEASURE(S) Leukocyte populations determined by immunohistochemical techniques, bacteriologic assessment of urine, and sperm density and motility. RESULT(S) The most cellular specimens were antegrade specimens obtained from men with SCIs and coexisting urinary tract infections. The highest proportion of leukocytes occurred in retrograde samples from men with SCIs and urinary tract infections. The most predominant leukocytes in all specimens were granulocytes. Infection increased the number of T cells and the degree of cell activation. There was no significant correlation between leukocyte populations and total motile sperm counts. CONCLUSION(S) Increased numbers of leukocytes in semen samples from men with SCIs are the result of urinary tract infections. The reduced sperm motility seen in men with SCIs does not correlate with the numbers of leukocytes; therefore, other factors also contribute to the semen abnormalities in these patients.

Concentration of Interleukin-12 in the peritoneal fluid is not influenced by the presence of endometriosis, its stage or the phase of the menstrual cycle

Background. IL‐12 is a key immunomodulatory cytokine. Its presence or concentration in peritoneal fluid is not related to the presence of endometriosis or the stage of the disease. A study was carried out to gain insight into the role of IL‐12 in the development and maintenance of endometriosis in relation to menstrual cycle.

Peritoneal fluid concentrations of interleukin‐4 in relation to the presence of endometriosis, its stage and the phase of the menstrual cycle

Background. Interleukin‐4 (IL‐4) is a cytokine with both stimulatory and inhibitory effects on the inflammatory system such as macrophage inhibition and T‐cell activation. It is known to regulate several monocyte functions, including inhibition of the synthesis of cytokines such as IL‐1, IL‐6 and TNF‐α as well as potentiating IL‐8.

Peritoneal fluid concentrations of interleukin-11 in women with endometriosis

OBJECTIVE To determine the peritoneal fluid concentrations of interleukin-11 (IL-11) in women with endometriosis as compared with the control group. DESIGN A prospective, controlled study. SETTING The obstetrics and gynecology department of a teaching hospital and a university immunology department. PATIENT(S) Sixty consecutive women undergoing laparoscopic surgery for benign gynecological indications. INTERVENTION(S) Peritoneal fluid was obtained during laparoscopy, and the concentration of IL-11 was measured. MAIN OUTCOME MEASURE(S) Concentration of IL-11 in correlation with the presence of endometriosis, its stage, and the phase of the menstrual cycle. RESULT(S) IL-11 was detectable in the peritoneal fluid of 64% of women tested. Concentrations of IL-11 showed no correlation with the presence of endometriosis, the American Fertility Society stage of the disease, or the phase of the menstrual cycle. CONCLUSION(S) We found no evidence to suggest that IL-11 is involved in the pathogenesis of pelvic endometriosis.

ORIGINAL ARTICLE: The Role of Cytokine Expression in Different Subgroups of Subfertile Men: CYTOKINES AND MALE SUBFERTILITY

Problem  The aim of this study was to evaluate the levels of seminal plasma cytokines interleukin 6 (IL‐6), interleukin 8 (IL‐8), interleukin 10 (IL‐10), interleukin 11 (IL‐11), interleukin 12 (IL‐12), tumour necrosis factor alpha (TNF‐α) and interferon gamma (IFN‐γ) in male subfertility.