Abstract
Objective
To clarify the pathogenesis of sudden unexpected natural death (SUD) as well as biomarkers to differentiate the underlying diseases, by performing cytokine analysis in the acute phase of pediatric patients in whom viral infection led to SUD.
Methods
An acute phase cytokine analysis of pediatric patients in whom viral infection led to SUD was performed, and the data obtained were compared with those from SUD patients not associated with viral infections. Subjects included 4 boys aged 1–16 mo who died of cardiopulmonary arrest associated with viral infections. The causative viruses were identified as enterovirus, parainfluenza virus, respiratory syncytial virus, and rotavirus. The 4 other infants/children (aged 2–12 mo) died of non-infectious episodes, i.e., 1, 2, and 1 died of drowning, falling, and a traffic accident, respectively. Cerebrospinal fluid samples (CSF) of the subjects were collected during cardiopulmonary resuscitation or within 24 h of the events.
Results
The infection-induced sudden death group showed elevated CSF levels of inflammatory cytokines and chemokines. No increase was observed in interleukin-10 levels. Furthermore, in the infection-induced sudden death group, platelet-derived growth factor levels correlated with inflammatory cytokine levels.
Conclusions
Infection-associated SUD may be differentiated from noninfectious SUD by measuring the levels of acute phase–inflammatory cytokines and chemokines at the onset of SUD.
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References
Hirabayashi M, Yoshinaga M, Nomura Y, et al. Environmental risk factors for sudden infant death syndrome in Japan. Eur J Pediatr. 2016;175:1921–6.
Sutton RN, Emery JL. Sudden death in infancy: a microbiological and epidemiological study. Arch Dis Child. 1966;41:674–7.
Rambaud C, Guibert M, Briand E, et al. Microbiology in sudden infant death syndrome (SIDS) and other childhood deaths. FEMS Immunol Med Microbiol. 1999;25:59–66.
Bajanowski T, Rolf B, Jorch G, Brinkmann B. Detection of RNA viruses in sudden infant death (SID). Int J Legal Med. 2003;117:237–40.
Brooks EG, Gill JR, National Association of Medical Examiners NAME Ad Hoc Committee for Bioterrorism and Infectious Disease. Testing for infectious diseases in sudden unexpected infant death: a survey of medical examiner and coroner offices in the United States. J Pediatr. 2015;167:178–82.
Weber MA, Hartley JC, Ashworth MT, Malone M, Sebire NJ. Virological investigations in sudden unexpected deaths in infancy (SUDI). Forensic Sci Med Pathol. 2010;6:261–7.
Yagmur G, Ziyade N, Elgormus N, et al. Postmortem diagnosis of cytomegalovirus and accompanying other infection agents by real-time PCR in cases of sudden unexpected death in infancy (SUDI). J Forensic Legal Med. 2016;38:18–23.
Kawamura Y, Ohashi M, Ihira M, Hashimoto S, Taniguchi K, Yoshikawa T. Nationwide survey of rotavirus-associated encephalopathy and sudden unexpected death in Japan. Brain Dev. 2014;36:601–7.
Ito H, Osamura T, Nakajima F, et al. Survey of severe respiratory syncytial virus infection in Kyoto prefecture from 2003 to 2007. Pediatr Int. 2010;52:273–8.
Vennemann MM, Loddenkötter B, Fracasso T, et al. Cytokines and sudden infant death. Int J Legal Med. 2012;126:279–84.
Arima Y, Harada M, Kamimura D, et al. Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier. Cell. 2012;148:447–57.
Zhao H, Z Nie, L Zhu. The effect of hyperbaric oxygen on cytokine IL-10 in the brain tissues and blood-brain barrier after cerebral ischemia-reperfusion in mice. Chinese J Rehabilitation Med. 2008;23(2):110–3.
Argaw AT, Gurfein BT, Zhang Y, Zameer A, John GR. VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc Natl Acad Sci U S A. 2009;106:1977–82.
Jones KL, Krous HF, Nadeau J, Blackbourne B, Zielke HR, Gozal D. Vascular endothelial growth factor in the cerebrospinal fluid of infants who died of sudden infant death syndrome: evidence for antecedent hypoxia. Pediatrics. 2003;111(2):358–63.
Ma Q, Huang B, Khatibi N, et al. PDGFR-α inhibition preserves blood-brain barrier after intracerebral hemorrhage. Ann Neurol. 2011;70:920–31.
Goldwater PN. SIDS pathogenesis: pathological findings indicate infection and inflammatory responses are involved. FEMS Immunol Med Microbiol. 2004;42(1):11–20.
Pryce JW, Bamber AR, Ashworth MT, Klein NJ, Sebire NJ. Immunohistochemical expression of inflammatory markers in sudden infant death; ancillary tests for identification of infection. J Clin Pathol. 2014;67(12):1044–51.
Moscovis SM, Gordon AE, Al Madani OM, et al. Virus infections and sudden death in infancy: the role of interferon-r. Front Immunol. 2015;6:107.
Blackwell CC, Moscovis SM, Gordon AE, et al. Exploring the risk factors for sudden infant deaths and their role in inflammatory responses to infection. Front Immunol. 2015;6:44.
Ferrante L, Opdal SH, Vege A, Rognum TO. Is there any correlation between HLA-DR expression in laryngeal mucosa and interleukin gene variation in sudden infant death syndrome? Acta Paediatr. 2013;102:308–13.
Ferrante L, Opdal SH. Sudden infant death syndrome and the genetics of inflammation. Front Immunol. 2015;6:63.
Blackwell CC, Moscovis SM, Gordon AE, et al. Cytokine responses and sudden infant death syndrome: genetic, developmental, and environmental risk factors. J Leukoc Biol. 2005;78:1242–54.
Acknowledgments
The present study was supported by a Grant-in-Aid for Scientific Research (20 K17909).
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All authors meet the ICMJE authorship criteria. SM managed and wrote the manuscript. SS and SN contributed to patient management as well as manuscript writing and proof reading. SS and GY contributed intellectually and helped with patient management and writing the manuscript. SM and YK helped with patient management. YK and SS managed virological and cytokine analyses. HK is the guarantor for this manuscript.
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Morichi, S., Suzuki, S., Nishimata, S. et al. Increased Platelet-Derived Growth Factor and Cytokine Levels in the Cerebrospinal Fluid of Patients of Sudden Unexpected Death with or without Viral Infection. Indian J Pediatr 88, 879–884 (2021). https://doi.org/10.1007/s12098-020-03588-2
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DOI: https://doi.org/10.1007/s12098-020-03588-2