The ratio of interleukin (IL)-18 to IL-12 secreted by peripheral blood mononuclear cells is increased in normal pregnant subjects and decreased in pre-eclamptic patients

Interleukin (IL)-18 acts in synergy with IL-12 to promote development of T helper 1 (Th1) responses. On the other hand, IL-18 alone has the capacity to induce Th2 responses. Here, we have measured IL-18 and IL-12 secretion by non-stimulated peripheral blood mononuclear cells (PBMC) from 17 non-pregnant women, 21 healthy pregnant women, 9 mildly pre-eclamptic patients and 15 severely pre-eclamptic patients. Th1/Th2 ratios in PBMC were determined by flow cytometry. PBMC from healthy pregnant subjects secreted more IL-18 and less IL-12 than non-pregnant women. PBMC from severely pre-eclamptic patients secreted more IL-12 than those from healthy pregnant women, while IL-18 secretion in mildly pre-eclamptic patients resembled that in normal pregnancy. The ratios of IL-18 to IL-12 were significantly higher in healthy pregnant women than non-pregnant women. These ratios were significantly lower in severely pre-eclamptic cases than in normal pregnancy subjects, while these ratios in mild pre-eclampsia resembled those in normal pregnancy. Interestingly, Th1/Th2 ratios were negatively correlated with the ratios of IL-18/IL-12. These results suggest that elevated IL-18 secretion and decreased IL-12 secretion by PBMC may induce Th2 dominance in normal pregnancy, while elevated secretion of both IL-18 and IL-12 by PBMC may cause Th1 dominance in severe pre-eclampsia.     

Polymorphisms of interleukin (IL)-1α, IL-1β, IL-6, IL-10, and IL-18 and the risk of ovarian cancer

OBJECTIVE: Recent studies of ovarian cancer have suggested a role for inflammation in carcinogenesis. Data from a population-based case-control study in Hawaii were examined to assess the relation between polymorphisms in cytokines involved with the inflammatory response, specifically members of the interleukin (IL) family and the incidence of ovarian cancer. PATIENTS AND METHODS: The analysis of 182 epithelial ovarian cancer cases and 219 controls focused on the polymorphisms in the following genes: IL-1alpha, IL-1beta, IL-6, IL-10, and IL-18. Genotype data were obtained from blood samples collected in participants' homes, and reproductive, demographic, and lifestyle histories were collected during interview. RESULTS: There were no significant odds ratios (ORs) for ovarian cancer by allelic variants in any of the IL genes after adjusting for age, ethnicity, education, oral contraceptive pill use, pregnancy, and history of tubal ligation. Although there was a significantly reduced risk of ovarian cancer risk among women with an IL-1alpha (-4845) T allele compared to women with two G alleles (OR: 0.59; 95% confidence interval: 0.37-0.97) after adjustment for age and ethnicity, the trend was not significant (p = 0.10). Further examination of the data suggested that women with at least one IL-18 variant allele (a G to C transition at position -137) were at significantly decreased risk of advanced ovarian cancer (OR: 0.51; 95% confidence interval: 0.28-0.90) compared to women with the IL-18 GG genotype. There was a significant difference in the risk of ovarian cancer associated with the IL-18 C allele by stage at diagnosis (p = 0.04 for homogeneity in the ORs): cases with IL-18 GC or CC genotypes were less likely to be diagnosed at regional/distant stages. Analysis of the data within ethnic subgroups revealed a significant positive association of the heterozygous IL-18 GC genotype with ovarian cancer risk among Native Hawaiian women (OR: 9.96; 95% CI: 1.88-52.90). The OR for ovarian cancer was not significant for Native Hawaiian women homozygous for the IL-18 C allele, but only one case and control had the IL-18 CC genotype. CONCLUSIONS: Overall, this study does not support an association of selected IL-1alpha, IL-1beta, IL-6, IL-10, or IL-18 polymorphisms with the risk for ovarian cancer. However, the IL-18 G137C variant may be a marker for ovarian cancer progression or metastasis.