Profound Deficit of IL10 at Birth in Children Who Develop Childhood Acute Lymphoblastic Leukemia

Abstract

Background Childhood acute lymphoblastic leukemia (ALL) may originate via abnormal immune responses to infectious agents. It is unknown whether prenatal immune development may differ in children who develop the disease. The current study examines the association between neonatal cytokine profiles, a proxy measure for a child's prenatal immune development, and childhood ALL. Methods Neonatal blood spots of 116 childhood ALL cases and 116 controls living in California were ascertained. Eleven cytokines associated with Th1, Th2, and Th17 lymphocytes were measured using a multiplex bead-based assay. Unconditional logistic regression was performed to estimate the odds ratio (OR) measuring the association between neonatal cytokines and ALL adjusted for age, sex, race/ethnicity, and household income. Results Of the 11 cytokines measured, 5 (IL4, IL6, IL10, IL12, and IL13) were detectable. Except for IL12, the other 4 cytokines were all significantly lower among cases compared to controls. In a multivariable model including the 5 cytokines, only IL10 remained independently associated with childhood ALL with an OR=0.04, 95% confidence interval: 0.01-0.18, comparing the highest tertile to the lowest tertile. Conclusions A child's neonatal level of IL10, a key regulator for modulating the intensity and duration of immune responses, is associated with his/her subsequent risk of developing ALL. Impact The current analysis shows that children with ALL may have a dysregulated immune function present at birth.

Mode of Delivery and Risk of Childhood Leukemia

“…Studies have shown that children developing any medically diagnosed infection (i.e., an infection leading to clinically fulminant symptoms) within the first year of life have an increased odds of developing common ALL (cALL) defined as ALL with expression of CD10 and CD19 surface antigens (pre-B-cell ALL) and diagnosis occurring between 2 and 5.9 years of age (9; 10). Recent work from our group showed significant differences in neonatal cytokines measured in Guthrie cards at birth between children who later contract ALL and controls (11). These findings suggest developmental differences in immune function might also contribute to development of disease.…”

IL-10 gene polymorphism and influence of chemotherapy on cytokine plasma levels in childhood acute lymphoblastic leukemia patients

“…Previously, Schulz, Munker, Ertl, Holler and Kolb [29] have evaluated the autocrine production of cytokines by leukemic cells, and demonstrated that ALL blasts express the mRNA for IL-10 and TNF-α. Chang, Zhou, Buffler, Chokkalingam, Metayer and Wiemels [30] showed that serum levels of IL-10 in children neonatal who developed ALL during childhood were significantly lower than in controls.…”

Cesarean Section and Chronic Immune Disorders

“…25 Reduced cytokine levels at birth have been associated with later development of allergy 26 and atopic predisposition, 27 and children who later developed childhood leukemia also had markedly reduced interleukin-10 levels at birth. 28 The birth setting around cesarean delivery is different from vaginal birth with respect to several factors including anesthetic agents and antibiotics during birth, physiologic effects on the newborn, and the hospital environment after birth. 29 It may be speculated that the effect from cesarean delivery is mediated by changes in the microbiome of the newborn.…”