The role of bacterial toxins in sudden infant death syndrome (SIDS).

There is increasing evidence for the involvement of bacterial toxins in some cases of sudden infant death syndrome (SIDS), particularly the pyrogenic toxins of Staphylococcus aureus. This had led to the hypothesis that some SIDS deaths are due to induction of inflammatory mediators by infectious agents or their products during a period in which the infant is unable to control these normally protective responses. The genetic, developmental and environmental risk factors identified for SIDS are assessed in relation to frequency or density of mucosal colonisation by toxigenic bacteria and their effects on induction and control of inflammatory responses to the toxins.

Why is smoking a risk factor for sudden infant death syndrome?

Smoking is a major risk factor for both Sudden Infant Death Syndrome (SIDS) and respiratory tract infections. Such infections, both viral and bacterial, also increase the SIDS risk. This study investigated the effect of cigarette smoke at two stages of infection: 1) mucosal surface colonization; 2) induction and control of inflammatory responses. For colonization, RSV or influenza A infected cells bound several bacterial species in significantly higher numbers due to increased expression of host cell antigens. Buccal epithelial cells from smokers bound significantly more bacteria. For Staphylococcus aureus, this was associated with increased tar levels. Some SIDS deaths have been proposed to result from high levels of pro-inflammatory mediators elicited by infection and/or cigarette smoke during a developmental period when infants are less able to control inflammatory responses. Inflammatory reponses were compared between blood samples from smokers (n = 42) and non-smokers (n = 60) stimulated with TSST-1 or LPS. Non-smokers had significantly higher IL-6 (P = 0.011), IFN (P = 0.003) and IL-10 (P = 0.000) baseline levels. Non-smokers had higher IFN (P = 0.008) and IL-1 (P = 0.001, 0.007) responses to LPS and higher IL-10 responses to TSST-1 (P < 0.05) and LPS (P < 0.000). This study highlights that smoking increases the SIDS risk by greater susceptibility to viral and bacterial infections and enhanced bacterial binding after passive coating of mucosal surfaces with smoke components. In animal models, IL-10 reduced the lethal effect of staphylococcal toxins. In this study, smokers had lower IL-10 responses toTSST-1 and LPS. Dose response effects of cigarette smoke exposure needs to be established in relation to inflammatory response control and infantile infections.

Evidence for a genetic component in sudden infant death syndrome.

There is increasing evidence that inflammatory responses have been elicited in some Sudden Infant Death Syndrome (SIDS) infants and that these responses are under genetic control. The objective of this study was to investigate the hypothesis that the cytokine responses of SIDS parents (n = 41) differed significantly from control donors (n = 61). Blood samples were stimulated with the staphylococcal toxin TSST-1 and LPS from Eschericia coli and assessed for production of TNF, IL-1, IL-6, IFN and IL-10. In response toTSST-1 (P < 0.02) and LPS (P < 0.002), SIDS parents produced higher levels of IL-1 than the controls. SIDS parents produced higher levels of IFN in response to TSST-1 compared to LPS (P < 0.001) although in response to LPS, the IFN (P = 0.0008) and IL-6 (P < 0.0002) responses of the SIDS parents were lower than those of the controls. For TNF and IL-10, there was little difference between the two groups unless the effect of smoking was considered. As part of this work, a small pilot genotyping study was carried out using DNA from SIDS parents (n = 10), control donors (n = 10) and Bangladeshi subjects (n = 10). An IFN polymorphism (3/3) was found in 40%,15.4% and 0% of donors respectively. Staphylococcal toxins have been identified in SIDS infants therefore this study highlights the importance of assessing IL-1 levels. Determination of cytokine polymorphisms and consideration of interactions between these and environmental factors such as smoking in high, average and low risk ethnic groups will assist in establishing the contribution of these factors to an infant's susceptibility to SIDS.