Variations in cytokine mRNA expression during normal human pregnancy

Abstract

Epidemiological data provide evidence that disease activity of T cell-mediated, organ-specific autoimmune diseases is reduced during pregnancy. Although there are several experimental animal studies on the effect of pregnancy on the immune system, the situation in humans is less clear. We therefore performed a prospective analysis of cytokine mRNA expression in whole blood by a new on-line reverse transcriptase-polymerase chain reaction technique and of serum hormone levels during pregnancy in healthy women. The control group included age-matched non-pregnant healthy women. Quantitativecytokine mRNA expression revealed significantly reduced IL-18, interferon-gamma (IFN-gamma), and IL-2 mRNA levels in the first and second trimester in pregnancy compared with non-pregnant women. No difference between groups was detected for tumour necrosis factor-alpha (TNF-alpha) mRNA. IL-4 and IL-10 mRNA were detected at low levels in only 20% of pregnant women and were reduced to a statistically significant extent in the second and third trimester compared with the control group. Changes in IL-18 mRNA expression correlated inversely with serum values for human choriogonadotropin (HCG) and IL-10 serum levels correlated with increases in serum 17beta-oestradiol levels. These data indicate immunomodulatory effects of pregnancy at the cytokine level which may be related to the variations in the clinical course of organ-specific, T cell-mediated autoimmune diseases during pregnancy.

Recurrent miscarriages: What is the role of cytokines?

“…This is substantiated by the evidence that pregnancy tends to ameliorate pre-existing autoimmune cell-mediated conditions [22]. In normal pregnant women, there is significantly higher IL-10 and other Th2 cytokine production by mitogenactivated peripheral blood mononuclear cells [29,30] and reduced IL-2 [27] and IFN-g mRNA expression [31] and their corresponding CD4 þ and CD8 þ Tcells [32].…”

Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: Determinations of a panel of nine cytokines in clinical sample culture supernatants

“…The shift from Th1 cytokine production to Th2 cytokine production protects the semi-allogeneic fetus from rejection by the maternal immune system, but as gestation progresses a shift from a predominate Th2 response to a Th1 response occurs (Raghupathy et al, 2000). Poor reproductive outcomes such as preterm delivery and fetal loss have been associated with a Th1 bias (Balkanli-Kaplan et al, 2004;Kwak-Kim et al, 2003;Chaouat et al, 2003;Raghupathy et al, 2000;Kruse et al, 2000;Darmochwal-Kolarz et al, 1999), although this is not a uniform observation (Sakai et al, 2004;Zenclussen et al, 2002). This highly complex interaction between the reproductive system, pregnancy, other pathologic processes, and the immune system is gradually being elucidated.…”

Human chorionic gonadotropin is an immune modulator and can prevent autoimmune diabetes in NOD mice

“…The symptoms of autoimmune diseases such as rheumatoid arthritis, Crohn's disease and multiple sclerosis are attenuated during pregnancy [2][3][4]. In pregnant women, the expression of T helper (Th)1 cytokine mRNA such as IL2 and IFN-γ (also known as IFNG) is significantly decreased, while expression of IL18 mRNA, an inducer of IFN-γ in T lymphocytes and natural killer cells, is inversely correlated with serum levels of hCG [5]. This suggests that hCG may have an immunoregulatory role in addition to its classical reproductive role in the maintenance of pregnancy.…”