Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy

Abstract

SUMMARYAntigen-and mitogen-stimulated cytokine production by peripheral blood mononuclear cells (PBMC) of 50 pregnant women and 31 age-and sex-matched non-pregnant controls were analysed to determine whether changes in cytokine production occur during normal and pathologic human gestation. The pregnant women, consecutively enrolled during a 3-month period, were undergoing a normal, nonpathologic pregnancy at the time of entry into the study, and underwent ultrasound examination to ascertain the exact week of pregnancy and the vitality of the fetus. Forty of the 50 pregnancies (80%) terminated physiologically with the birth of normal babies. Spontaneous abortions were observed in 5/50 (10%) women, and five women gave birth to newborns small for gestational age (SGA). A decrease in the production of IL-2 and interferon-gamma (IFN-°) accompanied by an increase in production of IL-4 and IL-10, was observed in normal pregnancy, with the lowest quantities of IL-2 and IFN-°and the highest quantities of IL-4 and IL-10 present in the third trimester of pregnancy. Statistically significant increased production of both IL-2 and IFN-°and reduced production of IL-10 characterized pathologic pregnancies and distinguished them from normal pregnancies. These preliminary data suggest that a type 2 cytokine profile may be associated with normal human pregnancy, whereas the lack of a dominant type 2 cytokine profile may be indicative of a pathologic pregnancy.

Pro- and antiinflammatory cytokines in threatened miscarriages

“…IFN␥ production by peripheral lymphocytes in very early pregnancy is higher in normal women compared with women with recurrent miscarriage. 42 By contrast, IL-10 is known to be an antiinflammatory cytokine, 45 and as shown in our study and others, 46,47 high levels of IL-10 are associated with successful outcome. We also found that, when the ratios of Th1/Th2 cytokines were calculated, there was a shift towards Th1 cytokines with elevated TNF␣/IL-10 and IFN␥/ IL-10 ratios in patients with TM who subsequently miscarried.…”

Associations of maternal immune response with MeHg exposure at 28 weeks’ gestation in the Seychelles Child Development Study

“…59 This change is considered important for a healthy term pregnancy. 9,10 Although we did not see any overall association with Th2, we did observe lower concentrations of IL-4 and IL-10 with increasing concentrations of MeHg at 28 weeks gestation. In pregnancy, IL-10 is an important immunoregulatory cytokine produced by cytotrophobloasts at the materno-fetal interface acting to maintain the balance between humoral and inflammatory responses.…”

“…2,8 In the second trimester, Th2 cells secrete predominantly anti-inflammatory cytokines including interleukin (IL)-4, IL-5 and IL-10 which, in combination with a reduction in inflammatory Th1 cytokines IL-1β, IL-2 and interferon gamma (IFN)-γ, have been associated with healthy term pregnancy. 9,10 Therefore, specific balance between maternal pro-inflammatory and anti-inflammatory cytokines throughout pregnancy is believed to be critical for the success of a pregnancy and favourable birth outcomes. 11 The normal variation, however, in the magnitude of these immunologic changes during pregnancy has not been fully defined.…”

Two cases of eosinophilic pustular folliculitis associated with pregnancy

“…It is reported that successful pregnancy is a Th2‐related phenomenon 3. To our knowledge, six cases of EPF associated with pregnancy have been reported in the published work.…”

“…In one of ours (case 1), EPF developed after the start of the first pregnancy and relapsed during the second pregnancy. Although further information is needed, these may indicate that pregnancy and EPF are correlated through Th2‐type immune responses 2, 3…”