Hamano H.a· Takahashi K.a· Kimura S.a,b· Matsuguma C.a· Kaneyasu H.a· Fujimoto Y.a· Ohta N.b· Okada S.a· Hasegawa S.a

Author affiliations

aDepartment of Pediatrics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
bDivision of Neonatology, Yamaguchi Prefectural Grand Medical Center, Yamaguchi, Japan

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Article / Publication Details

First-Page Preview

Received: December 01, 2022
Accepted: February 09, 2023
Published online: March 30, 2023

Number of Print Pages: 10
Number of Figures: 4
Number of Tables: 2

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: https://www.karger.com/NEO

Abstract

Introduction: Interleukin (IL)-33 and its receptor ST2L play key roles in the IL-33/ST2 signaling pathway. Soluble ST2 (sST2) inhibits the proper function of IL-33. sST2 levels are increased in patients with several neurological diseases, but in infants with hypoxic-ischemic encephalopathy (HIE), IL-33 and sST2 levels have not been studied. This study aimed to investigate whether serum levels of IL-33 and sST2 are useful as biomarkers of HIE severity and prognostic factors for infants with HIE. Methods: Twenty-three infants with HIE and 16 controls (gestational age ≥36 weeks and ≥1,800 g birth weight) were enrolled in this study. Serum levels of IL-33 and sST2 were measured at <6 h, 1–2, 3, and 7 days of age. Hydrogen-1 magnetic resonance spectroscopy was performed, and ratios of peak integrals of lactate/N-acetylaspartate (Lac/NAA) were calculated as objective indicators of brain damage. Results: In the moderate and severe HIE, serum sST2 concentrations were increased and there was a good correlation between serum sST2 and HIE severity on days 1–2, whereas no variation was observed in serum IL-33. Serum sST2 levels were positively correlated with Lac/NAA ratios (Kendall’s rank correlation coefficient = 0.527, p = 0.024), and both sST2 and Lac/NAA ratios were significantly higher in HIE infants with neurological impairment (p = 0.020 and <0.001, respectively). Conclusions: sST2 may be a useful predictor of severity and later neurological outcomes in infants with HIE. Further investigation is required to elucidate the relationship between the IL-33/ST2 axis and HIE.

© 2023 S. Karger AG, Basel

References Shankaran S, Woldt E, Koepke T, Bedard MP, Nandyal R. Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants. Early Hum Dev. 1991 May;25(2):135–48. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976 Oct;33(10):696–705. Simon NP. Long-term neurodevelopmental outcome of asphyxiated newborns. Clin Perinatol. 1999 Sep;26(3):767–78. Chavez-Valdez R, Miller S, Spahic H, Vaidya D, Parkinson C, Dietrick B, et al. Therapeutic hypothermia modulates the relationships between indicators of severity of neonatal hypoxic ischemic encephalopathy and serum biomarkers. Front Neurol. 2021 Nov 2;12:748150. Tagin MA, Woolcott CG, Vincer MJ, Whyte RK, Stinson DA. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2012 Jun 1;166(6):558–66. Douglas-Escobar MV, Heaton SC, Bennett J, Young LJ, Glushakova O, Xu X, et al. UCH-L1 and GFAP serum levels in neonates with hypoxic-ischemic encephalopathy: a single center pilot study. Front Neurol. 2014 Dec 19;5:273. Alderliesten T, de Vries LS, Benders MJNL, Koopman C, Groenendaal F. MR imaging and outcome of term neonates with perinatal asphyxia: value of diffusion-weighted MR imaging and 1H MR spectroscopy. Radiology. 2011 Oct;261(1):235–42. Takahashi K, Hasegawa S, Maeba S, Fukunaga S, Motoyama M, Hamano H, et al. Serum tau protein level serves as a predictive factor for neurological prognosis in neonatal asphyxia. Brain Dev. 2014 Sep;36(8):670–5. Orrock JE, Panchapakesan K, Vezina G, Chang T, Harris K, Wang Y, et al. Association of brain injury and neonatal cytokine response during therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy. Pediatr Res. 2016 May;79(5):742–7. Korhonen P, Kanninen KM, Lehtonen Š, Lemarchant S, Puttonen KA, Oksanen M, et al. Immunomodulation by interleukin-33 is protective in stroke through modulation of inflammation. Brain Behav Immun. 2015 Oct;49:322–36. Fairlie-Clarke K, Barbour M, Wilson C, Hridi SU, Allan D, Jiang HR. Expression and function of IL-33/ST2 axis in the central nervous system under normal and diseased conditions. Front Immunol. 2018 Nov 20;9:2596. Lüthi AU, Cullen SP, McNeela EA, Duriez PJ, Afonina IS, Sheridan C, et al. Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity. 2009 Jul 17;31(1):84–98. Jiao M, Li X, Chen L, Wang X, Yuan B, Liu T, et al. Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury. J Neuroinflammation. 2020 Aug 28;17(1):251. Du Q, Weng JF, Luo LF, Cen M, Yu WH, Zheng YK, et al. Serum ST2 as a potential prognostic biomarker for traumatic brain injury. Clin Chim Acta. 2018 Dec;487:145–52. Yanagisawa K, Takagi T, Tsukamoto T, Tetsuka T, Tominaga SI. Presence of a novel primary response gene ST2L, encoding a product highly similar to the interleukin 1 receptor type 1. FEBS Lett. 1993 Feb 22;318(1):83–7. Weinberg EO, Shimpo M, De Keulenaer GW, MacGillivray C, Tominaga SI, Solomon SD, et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation. 2002 Dec 3;106(23):2961–6. Bhardwaj A, Januzzi JL Jr. ST2: a novel biomarker for heart failure. Expert Rev Mol Diagn. 2010 May;10(4):459–64. Watanabe M, Nakamoto K, Inui T, Sada M, Honda K, Tamura M, et al. Serum sST2 levels predict severe exacerbation of asthma. Respir Res. 2018 Sep 3;19(1):169. Andersson C, Preis SR, Beiser A, DeCarli C, Wollert KC, Wang TJ, et al. Associations of circulating growth differentiation factor-15 and ST2 concentrations with subclinical vascular brain injury and incident stroke. Stroke. 2015 Sep;46(9):2568–75. Kanda M, Ohto-Ozaki H, Kuroiwa K, Tominaga S, Watanabe E, Iwahana H. Elevation of ST2 protein levels in cerebrospinal fluid following subarachnoid hemorrhage. Acta Neurol Scand. 2006 May;113(5):327–33. Du LX, Wang YQ, Hua GQ, Mi WL. IL-33/ST2 pathway as a rational therapeutic target for CNS diseases. Neuroscience. 2018 Jan 15;369:222–30. Mu R, Huang HQ, Li YH, Li C, Ye H, Li ZG. Elevated serum interleukin 33 is associated with autoantibody production in patients with rheumatoid arthritis. J Rheumatol. 2010 Oct;37(10):2006–13. Akamatsu T, Sugiyama T, Aoki Y, Kawabata K, Shimizu M, Okazaki K, et al. A pilot study of soluble form of LOX-1 as a novel biomarker for neonatal hypoxic-ischemic encephalopathy. J Pediatr. 2019 Mar;206:49–55.e3. Sun Y, Wen Y, Wang L, Wen L, You W, Wei S, et al. Therapeutic opportunities of interleukin-33 in the central nervous system. Front Immunol. 2021 May 17;12:654626. Article / Publication Details

First-Page Preview

Received: December 01, 2022
Accepted: February 09, 2023
Published online: March 30, 2023

Number of Print Pages: 10
Number of Figures: 4
Number of Tables: 2

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: https://www.karger.com/NEO

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