High-dose of intravenous immunoglobulin modulates immune tolerance in premature infants

BACKGROUND Intravenous immunoglobulin (IVIG) is commonly used to improve the immunomodulatory effects, although its regulatory effect on premature Treg cells is unclear. The purpose of this study is to study the effect of high dose of IVIG (HD-IVIG) on Treg cells expression and cytokine profile in premature birth. METHODS Fifty-two premature infants were enrolled in this study and thirty-one premature infants who were suspected to have intrauterine infection received HD-IVIG (1-2 g/kg) at the first day of birth; the remaining 21 premature infants were assigned as the control group. The peripheral blood CD4 + T and foxp3+ Treg cells were checked by flow cytometry, and cytokine concentrations were detected by cytometric bead array. RESULTS With the gestational age growth, peripheral blood CD4 + T and foxp3+ Treg cells of prematurity gradually declined from 50% to 35% and from 8% to 6%, respectively. Meanwhile, HD-IVIG increased the percentage of CD4 + T and foxp3+ Treg cells compared with their baseline levels (p < 0.001). HD-IVIG demonstrated different regulating effects on cytokines secretion, increased IL-17 and TGF-β, and inhibited IL-6 secretion. CONCLUSION Our results demonstrated that HD-IVIG not only enhanced the premature immune tolerance, but also suppressed the excessive inflammation response mediated by IL-6. TRIAL REGISTRATION This study was under the clinical study registration (ChiCTR-ORC-16008872, date of registration, 2016-07-21).