Sudden infant death syndrome, infection and inflammatory responses

Abstract

Sudden infant death syndrome (SIDS) is sudden unexpected death in infancy for which there is no explanation after review of the history, a death scene investigation and a thorough autopsy. The use of common diagnostic criteria is a prerequisite for discussing the importance of infection, inflammatory responses and trigger mechanism in SIDS. Several observations of immune stimulation in the periphery and of interleukin-6 elevation in the cerebrospinal fluid of SIDS victims explain how infections can play a role in precipitating these deaths. Finally, these findings and important risk factors for SIDS are integrated in the concept of a vicious circle for understanding the death mechanism. The vicious circle is a concept to elucidate the interactions between unfavourable factors, including deficient auto-resuscitation, and how this could result in death.

Gene variants predisposing to SIDS: current knowledge

“…Approximately half of the SIDS victims are reported to have symptoms of a slight upper airway infection prior to death [6], and the mucosal immune system is stimulated compared to victims of sudden violent death [8][9][10]. The observation by Vege et al [11] that half of the SIDS victims had IL-6 levels in the cerebrospinal fluid (CSF) in the same range as infants that died from infections such as meningitis and septicemia supported the view that the brain is the target organ for a lethal mechanism initiated by an immune reaction [10,12]. A link between the mucosal immune system and the central nervous system (CNS) was furthermore demonstrated by Vege et al [13] showing that both increased expression of HLA-DR antigens in glandular epithelium and increased number of IgA immunocytes in the laryngeal mucosa were significantly related to high IL-6 levels in the CSF.…”

Sudden Infant Death Syndrome: Review of implicated genetic factors

“…The other class of infectionrelated genes that has been frequently studied in SIDS is cytokines due to the evidence for inflammatory responses, particularly in the respiratory tract, in SIDS [reviewed in Goldwater, 2004;Vege and Rognum, 2004]. Cytokines are a large class of molecules that play a key regulatory roles in inflammation and immune response; the risk of acquiring infection and the risk of developing severe complications are related to genetic variability in cytokine genes, particularly IL10 [see e.g., pneumonia, Gallagher et al, 2003; Epstein-Barr virus infection, Helminen et al, 2001].…”

The Sudden Infant Death Syndrome

“…26 A causal role for mild infection in sudden infant death is suggested by reports that in approximately half of SIDS cases, the infants have a seemingly trivial infection around the time of death, as well as mild tracheobronchial inflammation and altered serum immunoglobulin or cytokine levels and the presence of microbial isolates at autopsy. 27,28 In infants who die unexpectedly of infection, the given organism may precipitate a lethal cytokine cascade or toxic response. 27 If all specific causes of infant death are delineated, the designations SUID and SIDS will no longer be needed.…”

“…2 In the ensuing years, all SIDS hypotheses essentially invoked defective respiratory or autonomic mechanisms. 27,30,[51][52][53][54][55][56][57][58] The roles of respiratory and autonomic pathways in SIDS are not mutually exclusive, given that infants who subsequently died of SIDS have frequently been found to have subclinical deficits in both respiratory and autonomic function. [59][60][61] Ultimately, SIDS appears to involve failed defense mechanisms, with sleep in some important way unmasking the underlying vulnerability.…”