Interleukin-19 in fetal systemic inflammation

Abstract

Objective: The fetal inflammatory response syndrome (FIRS) is considered the fetal counterpart of the systemic inflammatory response syndrome (SIRS), which can be caused by infection and non-infection-related insults. Although the initial response is mediated by pro-inflammatory signals, the control of this response is achieved by anti-inflammatory mediators which are essential for the successful outcome of the affected individual. Interleukin (IL)-19 is capable of stimulating the production of IL-10, a major anti-inflammatory cytokine, and is a potent inducer of the T-helper 2 (Th2) response. The aim of this study was to determine if there is a change in umbilical cord plasma IL-19 and IL-10 concentrations in preterm neonates with and without acute funisitis, the histologic counterpart of FIRS. Methods: A case-control study was conducted including 80 preterm neonates born after spontaneous labor. Neonates were classified according to the presence (n = 40) or absence of funisitis (n = 40), which is the pathologic hallmark of FIRS. Neonates in each group were also matched for gestational age. Umbilical cord plasma IL-19 and IL-10 concentrations were determined by ELISA. Results: 1) The median umbilical cord plasma IL-19 concentration was 2.5-fold higher in neonates with funisitis than in those without funisitis (median 87 pg/mL; range 20.6–412.6 pg/mL vs. median 37 pg/mL; range 0–101.7 pg/mL; p < 0.001); 2) newborns with funisitis had a significantly higher median umbilical cord plasma IL-10 concentration than those without funisitis (median 4 pg/mL; range 0–33.5 pg/mL vs. median 2 pg/mL; range 0–13.8 pg/mL; p < 0.001); and 3) the results were similar when we included only patients with funisitis who met the definition of FIRS by umbilical cord plasma IL-6 concentrations ≥ 17.5 pg/mL (p < 0.001). Conclusion: IL-19 and IL-10 are parts of the immunologic response of FIRS. A subset of fetuses with FIRS had high umbilical cord plasma IL-19 concentrations. In utero exposure to high systemic concentrations of IL-19 may reprogram the immune response.

Keywords::

• Fetal inflammatory response syndrome (FIRS)
• chorioamnionitis
• funisitis
• anti-inflammatory limb
• IL-10
• preterm repture of membranes (PROM)
• childhood asthma
• SIDS
• prematurity
• preterm labor
• immune programming

Acknowledgement

This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. Presented at the 56^th Annual Meeting of the Society for Gynecologic Investigation, March 16–19, 2011, Miami, FL

Declaration of Interest: The authors declare no conflicts of interest exist.