Interleukin-12 (IL12; formerly NKSF, for natural killer cell stimulatory factor, or CLMF, for cytotoxic lymphocyte maturation factor) is a novel cytokine cloned from B-cell lines. It has a broad array of potent biologic activities, acting at picomolar and subpicomolar levels on both T and NK cells. IL12 is a disulfide-linked heterodimer composed of unrelated 40-kD (p40, or IL12B; 161561) and 35-kD (p35) subunits.
NCBI Summary:
This gene encodes a subunit of a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-independent induction of interferon (IFN)-gamma, and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity. [provided by RefSeq, Jul 2008]
General function
Ligand, Cytokine
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Cellular localization
Secreted
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Ovarian function
Early embryo development
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Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis. Singh AK et al. (2016) The study aimed to investigate key intrafollicular prognostic factors among various cytokines and angiogenic molecules for prediction of mature oocytes and good-quality embryos in women with endometriosis undergoing in vitro fertilization (IVF). Paired follicular fluid and serum samples were collected from 200 women with advanced stage endometriosis and 140 normal ovulating women during oocyte retrieval. The concentrations of cytokines (pro-inflammatory: IL-1β, TNF-α, IL-2, IL-8, IL-12, IFN-γ; anti-inflammatory: IL-4, IL-6, IL-10) and angiogenic molecules (vascular endothelial growth factor (VEGF), adrenomedullin, angiogenin) were determined in follicular fluid and serum using ELISA. Expression of these molecules was subjected to multivariate analysis for the identification of major predictive markers of oocyte and embryo quality. Receiver operating characteristic (ROC) curve was applied to determine the best cutoff point for the discrimination between mature and immature oocytes in these women. Significant increases in levels of cytokines and angiogenic molecules were observed in women with endometriosis compared to controls (P < 0.001). From the validated partial least squares-discriminant analysis (PLS-DA) model, IL-8, IL-12, and adrenomedullin were identified as the most important factors contributing to endometriosis and were negatively associated with oocyte maturity and embryo quality. The levels of IL-8, IL-12, and adrenomedullin may be good indicators of embryo and oocyte quality in endometriosis patients undergoing IVF. Further studies are necessary to ascertain the potential of these markers for oocyte and embryo developmental competence which may help improve the chances of a successful IVF in endometriosis patients.//////////////////
Follicular Proinflammatory Cytokines and Chemokines as Markers of IVF Success. Sarapik A et al. Cytokines are key modulators of the immune system and also contribute to regulation of the ovarian cycle. In this study, Bender MedSystems FlowCytomix technology was used to analyze follicular cytokines (proinflammatory: IL-1, IL-6, IL-18, IFN-?, IFN-a, TNF-a, IL-12, and IL-23;, and anti-inflammatory: G-CSF), chemokines (MIP-1a, MIP-1, MCP-1, RANTES, and IL-8), and other biomarkers (sAPO-1/Fas, CD44(v6)) in 153 women undergoing in vitro fertilization (IVF). Cytokine origin was studied by mRNA analysis of granulosa cells. Higher follicular MIP-1a and CD44(v6) were found to correlate with polycystic ovary syndrome, IL-23, INF-?, and TNF-a with endometriosis, higher CD44(v6) but lower IL- and INF-a correlated with tubal factor infertility, and lower levels of IL-18 and CD44(v6) characterized unexplained infertility. IL-12 positively correlated with oocyte fertilization and embryo development, while increased IL-18, IL-8, and MIP-1 were associated with successful IVF-induced pregnancy.
Expression regulated by
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Ovarian localization
, Follicular Fluid
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Expression of CD11c+HLA-DR+dendritic cells and related cytokines in the follicular fluid might be related to pathogenesis of ovarian hyperstimulation syndrome. Shi SL et al. (2016) To explore the expressions of CD11c+HLA-DR+dentritic cells in the follicular fluid of patients with OHSS and their significances. 100 individuals. embryos were observed. The distribution of dentritic cells in follicular fluid and the levels of IL-10, IL-12, IL-18 and IL-23 in follicular fluid were detected. There were ovarian hyperstimulation syndrome (OHSS) group and control group in this study. The OHSS group consisted of 50 patients with OHSS and the control group consisted of 50 patients who underwent in vitro fertilization-embryo transfer (IVF-ET) only due to male factors. The statuses of embryos were compared between the two groups. The distribution of dentritic cells in follicular fluid was determined with flow cytometry, and the levels of IL-10, IL-12, IL-18 and IL-23 in follicular fluid were detected with enzyme-linked immunosorbent assay (ELISA) in all patients. The two-pronuclear (2PN) fertility rate, high-quality embryo rate and available embryo rate were all significantly lower in OHSS group than in control group (all P<0.05). The number of CD11c+HLA-DR+dentritic cells (P<0.05) and the levels of IL-10, IL-12, IL-18 and IL-23 were all significantly higher in OHSS group than in control group (all P<0.01). The follicular fluid of the patients with OHSS is in an inflammatory status, the inflammatory status may be involved in OHSS and the microenvironment of follicular fluid may affects oocyte quality and embryo development.//////////////////
Gallinelli A, et al reported the correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome.
To investigate a possible correlation between interleukin-12 (IL-12) and IL-13 levels and lymphocyte subsets in the preovulatory follicles of patients with and without polycystic ovarian syndrome (PCOS). Seventy-eight infertile women undergoing IVF-embryo transfer.The subjects underwent blood sampling, ovum retrieval, and embryo transfer.Follicular fluid levels of T, androstenedione (A); IL-12, IL-13, activated T cells, T helper, and T-suppressor lymphocytes.The level of IL-12 detected in follicular fluid (FF) was significantly lower in patients with PCOS than in normally ovulating women (mean: 1.47 +/- 0.3 pg/mL vs. 2.25 +/- 0.7 pg/mL, respectively); in contrast, FF IL-13 concentrations were significantly higher in the patients with PCOS than in the normally ovulating women (mean: 32.5 +/- 3.7 pg/mL vs. 19.6 +/- 2.5 pg/mL, respectively), as was the total number of activated T lymphocytes (11.5% +/- 1.5% vs. 4.8% +/- 0.4%). A significant correlation was observed between FF activated T-cell concentrations and FF IL-12, IL-13, T, and A levels. No significant differences were observed when these data were compared with embryological parameters.The present study shows significant differences in the correlation between FF IL-12 and IL-13 levels and T lymphocyte numbers in the subset of patients with PCOS as compared to normally ovulating women.