Changes in cytokine production during pregnancy in patients with Graves' disease.

In order to investigate the role of type 1 and type 2 cytokines in the remission of Graves' disease (GD) during pregnancy, spontaneous and mitogen-stimulated production of interleukin (IL)-4, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), and tumour necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunospot assay of peripheral blood mononuclear cells from 10 pregnant women with GD, 8 healthy pregnant women, and 10 healthy nonpregnant women. Tests were performed in the first, second, and third trimesters of pregnancy and 10-17 weeks after delivery. IL-4 production was not affected greatly by normal or GD pregnancy, whereas IFN-gamma production was suppressed throughout pregnancy but returned to normal levels after delivery in both controls and patients. IL-6 and TNF-alpha tended to be higher in GD pregnancy than normal pregnancy, especially in the second and third trimesters. Controls had raised IL-10 in the first trimester with a return to normal levels by the third trimester, whereas patients had raised levels throughout pregnancy. IL-12 levels were suppressed to a greater extent in control than Graves' pregnancy, especially during the second and third trimesters. Ratios of IL10:IL12 in phytohemaglutinin (PHA)-stimulated cultures were much lower in GD than normal pregnancy and cross-regulation of IL-10 and IL-12 may be deficient in GD.