A dose-response between progressively increasing levels of interleukin-6 in the umbilical cord and histologic funisitis

Abstract

OF INTERLEUKIN-6 IN THE UMBILICAL CORD AND HISTOLOGIC FUNISITIS ROBERT MITTENDORF, SUSAN JANECZEK, MEGAN KOH, WILLIAM MACMILLAN, ROBERTA KARLMAN, RICHARD BESINGER, JOHN GIANOPOULOS, PETER G. PRYDE, Loyola University Chicago, Obstetrics and Gynecology, Maywood, IL University of Wisconsin, Obstetrics and Gynecology, Madison, WI OBJECTIVE: To determine whether a dose-response relationship exists between increasing levels of circulating interleukin-6 (IL-6) in the fetus at delivery and histologic funisitis. STUDY DESIGN: The Magnesium and Neurologic Endpoints Trial (MagNET), was a clinical trial designed to study fetal and neonatal outcomes subsequent to spontaneous preterm labor. During the conduct of the trial, numerous biological specimens were collected including: a) umbilical cord venous plasma for the determination of circulating fetal IL-6 levels at delivery using standard ELISA (Endogen, Cambridge, Mass.), and b) placental/cord histology to determine the presence of funisitis (transmural migration of neutrophils into the walls of umbilical cord blood vessels). RESULTS: There were 101 babies in the study for whomboth IL-6 levels and placental pathology could be matched. Among these, 17% (17/101) had funisitis and 36% (36/101) had increased IL-6 levels (>25 pg/ml). Of those with funisitis, specific IL-6 levels were: 25 pg/ml or less, n = 1; 32 pg/ml, 32, 47, 56, 118, 118, 154, 249, 272, 337, 366, 762, 2557, 4630, 4630, and 7780 pg/ml; for those without funisitis, the levels were: 25 pg/ml or less, n = 64; 33 pg/ml, 40, 40, 41, 65, 85, 87, 106, 129, 147, 199, 225, 236, 476, 538, 962, 1669, 2010, 2976 and 8660 pg/ml. Crosstabulating categories of IL-6 levels (0-25, 26-50, 51-75, 76-100, and >100 pg/ml) by funisitis status (see Table), we found there was a statistically significant dose-response relationship between increased circulatory levels of IL6 in the fetus at delivery and histologic funisitis (Cochran-Armitage trend test, P < .001). CONCLUSION: A dose-response between IL-6 and increased prevalence of funisitis suggests that the latter may be a late development in the evolution of Fetal Inflammatory Response Syndrome (FIRS). Furthermore, it may account for the fact that funisitis appears to be a more specific predictor of adverse outcomes than IL-6.