Cytokine responses and sudden infant death syndrome: genetic, developmental, and environmental risk factors

Abstract

Despite the success of the campaigns to reduce the risk of sudden infant death syndrome (SIDS), it still remains the major cause of postneonatal mortality. The incidence of SIDS is higher among ethnic groups in which there are also high incidences of serious infectious diseases. The risk factors for SIDS parallel those for susceptibility to infection, and recent data have provided evidence to support the mathematical model of the common bacterial toxin hypothesis. One current hypothesis for the etiology of SIDS is that the deaths are a result of overwhelming proinflammatory responses to bacterial toxins; as in inflammatory responses to sepsis, cytokines, induced by bacterial toxins, cause physiological changes leading to death. The genetic, developmental, and environmental risk factors for SIDS are reviewed in relation to colonization by potentially harmful bacteria and the inflammatory responses induced in the nonimmune infant to microorganisms or their products.

Hyper innate responses in neonates lead to increased morbidity and mortality after infection

“…Necrotizing enterocolitis, an intestinal disease that occurs frequently in preterm newborns, is thought to be due to a robust intestinal epithelial inflammatory responses to bacterial infection (9). Sudden infant death syndrome (SIDS) is another newbornrelated disease, and both infections in the 2 weeks before death occur in Ͼ40% of SIDS infants and increased IL-6 in the cerebrospinal fluid have been reported (41)(42)(43).…”

Review of immunological and virological aspects as contributory factors in Sudden Unexpected Death in Infancy (SUDI)

“…It is the principal cytokine secreted during the acute-phase inflammatory responses to damage in tissues. IL-6 has been found in high levels in some SIDS cases and infants who died of bacterial sepsis and meningitis [22,35,49]. The similar levels of IL-6 highlight possible similarities between SUDI cases and deaths due to infections and could support a contributory role of infections and subsequent immune response in causing SUDI.…”

“…The similar levels of IL-6 highlight possible similarities between SUDI cases and deaths due to infections and could support a contributory role of infections and subsequent immune response in causing SUDI. However, the degree of inflammation required for lethality is still uncertain [33,35,36].…”

“…Viral infections may act in combination with the immune response of the host to infection and the initiation of bacterial toxin production, thereby contributing to SIDS. Viruses also enhance cytokine activity, leading to unregulated expression of inflammatory mediators [22,35,36].…”

SIDS Risk Factors: Time for New Interpretations. The Role of Bacteria

“…The italics are ours, and it is to suggest that more is known than is suggested in this blank statement. We and our associates (Goldwater 2001, Bettelheim et al 1989,1990, Goldwater & Bettelheim 2002, Pearce et al 1999a, 1999b, 2004 as well as others (especially Drucker et al 1992, Bettiol et al 1994, Blackwell et al 2005, Jakeman et al 1991, Malam et al 1992, Sayers et al 1995 have shown that toxigenic organisms notably ones normally considered nonpathogenic commensals may well have an important role to play in the death of these infants. There is strong evidence to support the hypothesis that SIDS is triggered by a dysregulated response to infection or microbial toxins.…”