Carol Jenkins

Evidence of a TH 1 type response associated with recurrent miscarriage

OBJECTIVE To determine whether the T(H) 1 cytokine interferon (IFN)-gamma is associated with miscarriage whereas the T(H) 2 cytokine interleukin (IL)-10 is associated with successful pregnancy. DESIGN Controlled clinical study. SETTING Healthy volunteers in an academic setting. PATIENT(S) Group 1 comprised 10 nonpregnant women; group 2, 10 first-trimester primigravid women; group 3, 10 first-trimester primigravid women suffering spontaneous abortion; and group 4, 10 first-trimester pregnant women with a history of miscarriage. All women were pregnant at the time of sampling, but 5 miscarried later in the first trimester. INTERVENTION(S) None of the patients received any medication. MAIN OUTCOME MEASURE(S) Serum levels of IL-10 and IFN-gamma. RESULT(S) Levels of IL-10 were significantly raised in normal pregnancy. Levels of IFN-gamma were raised in the recurrent-miscarriage group as compared with normal pregnancy. When patients in group 4 were divided into those whose pregnancies went to term and those who miscarried, we found that successful pregnancy was associated with a statistically significant increase in IL-10, whereas miscarriage was associated with significantly increased levels of IFN-gamma. CONCLUSION(S) These results support the view that miscarriage is associated with a T(H) 1 type response.

Antioxidants: their role in pregnancy and miscarriage.

The aim of this study was to examine the role of antioxidants within the normal menstrual cycle, in healthy pregnancy, and in women suffering first-trimester miscarriage. The antioxidants chosen comprised of two from peripheral blood-plasma thiol and ceruloplasmin-and two extracellular parameters-superoxide dismustase (SOD) and red cell lysate thiol. We found that antioxidant levels varied little throughout the menstrual cycle. Pregnancies that went successfully to term were associated with increased levels of ceruloplasmin and SOD early in the first trimester. These changes were thought to offer the cell protection from the damage caused by the increased oxidative stress associated with pregnancy. First-trimester miscarriage was associated with significantly reduced levels of SOD. A subgroup of patients who miscarried in their first pregnancy, but whose second pregnancies were successful, had higher levels of plasma thiol and significantly reduced levels of red cell lysate thiol in the on-going pregnancy compared to levels at the time of miscarriage. Miscarriage and pregnancy appear to be associated with increased oxidative stress. In a successful pregnancy, however, changes occurred within the peripheral blood that offered protection from oxidant attack.

Abnormal First Trimester Serum Interleukin 18 Levels are Associated with a Poor Outcome in Women with a History of Recurrent Miscarriage

Problem:  How the maternal immune system adapts to tolerate the fetus is not fully understood, but a successful pregnancy is associated with the production of Th2‐type cytokines and miscarriage is associated with the production of Th1‐type cytokines.

Effects of high dose oestrogen therapy on circulating inflammatory markers

INTRODUCTION Whilst initial studies suggested HRT reduced the incidence of coronary heart disease, recent studies have suggested HRT increases cardiovascular risk. The route of HRT administration appears important with oral oestrogen significantly increasing levels of inflammatory markers and transdermal oestrogen causing no such changes. As the effects of the very high levels of oestrogen taken by male to female transsexuals are poorly understood this study has compared the changes occurring in circulating inflammatory markers following 6 months oral or transdermal oestrogen therapy. MATERIALS AND METHODS 23 patients (mean age 36+/-10 years) about to commence oral oestrogen were enrolled into Group 1. Group 2 comprised 7 patients (mean age 47+/-6 years) about to commence transdermal oestrogen. Plasma lipids (total cholesterol, triglyceride and HDL cholesterol); cytokines (IL-1, IL-6, IL-8, TNFalpha); antioxidants (superoxide dismutase, total nitric oxide, glutathione) and clotting factors (Factor V11, Factor V111, Factor 1X, fibrinogen) were measured after 0, 2, 4 and 6 months treatment. RESULTS No significant differences were found in plasma lipid levels. Group 1 patients showed significantly raised levels of IL-6, IL-1 and IL-8 during the first 2-4 months of treatment. Thereafter levels fell. Levels of SOD, FV11 and FV1X in Group 1 also increased over the study period. Patients receiving transdermal oestrogen showed elevated levels of GSH in the second month of treatment, but no significant changes in any of the other parameters measured. The rise in levels of IL-1 and Factor IX in the second month of treatment was significantly higher in the oral group than in the transdermal group. No other significant differences between the treatment groups were found. CONCLUSION Transsexual patients receiving oral oestrogen showed significant changes in inflammatory markers involved in the pathogenesis of vascular disease. No such changes were associated with transdermal oestrogen. Changes in two inflammatory markers were significantly greater than among patients receiving transdermal oestrogen.

Abnormal immunoglobulin subclass patterns in women with a history of recurrent miscarriage

OBJECTIVE To determine whether IgG subclass patterns differed between nonpregnant women, healthy pregnant women, and pregnant women with a history of recurrent miscarriage. DESIGN Controlled clinical study. SETTING An academic setting. PATIENT(S) Group 1 was comprised of 10 nonpregnant women, group 2 of 10 healthy pregnant women, group 3 of eight pregnant women with a history of recurrent miscarriage and whose pregnancies on this occasion went to term, and group 4 of 10 women with a history of recurrent miscarriage whose pregnancies again failed later in the first trimester. INTERVENTION(S) None of the patients received any medication. MAIN OUTCOME MEASURE(S) Serum levels of total IgG and IgG 1, 2, 3, and 4. RESULT(S) The results obtained showed that normal pregnancy was associated with a significant increase in total IgG production and an increase in IgG subclasses 1, 2, and 3. Women with a history of miscarriage, but who had a successful pregnancy on this occasion, showed a similar pattern of IgG subclasses. Women with a history of miscarriage and whose pregnancy again ended in miscarriage showed a different IgG subclass pattern. CONCLUSION(S) Pregnancies that ended in miscarriage showed a different pattern of IgG subclasses than those that continued to term. The changes seen in immunoglobulin patterns could be linked to changes in cytokine production.