Pyrogenic toxins of Staphylococcus aureus in sudden unexpected nocturnal deaths in adults and older children: factors influencing the control of inflammatory responses to toxic shock syndrome toxins

Sudden unexpected nocturnal deaths (SUND) occur in young immigrant workers, mainly from south-east Asia, who are employed in countries such as Singapo re and Saudi Arabia. Pyrogenic toxins of Staphylococcus aureus have been id entified in two cases of sudden unexpected death in adults in the UK and it has been suggested that these or other toxins with superantigen properties might induce strong inflammatory responses leading to sudden unexpected no cturnal deaths. The objectives of the present study were (1) to assess the levels of antibodies to pyrogenic staphylococcal toxins in the general popu lation, (2) to assess the levels of IgG to the toxins needed to reduce the production of inflammatory mediators by 50% in a model system, (3) to asses s in a model system the effects on inflammatory responses to toxic shock sy ndrome toxin-1 (TSST) of cortisol levels present at night, during the day a nd under conditions of physiological stress. Enzyme linked immunosorbent as says were used to assess levels of IgG to TSST, staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin C (SEC). Human buffy coats were used to examine the effect of IgG to the toxins for neutralising activity and t he effect of cortisol on induction of inflammatory mediators. Tumour necros is factor alpha (TNF-alpha) was detected by a bioassay with L929 cells, int erleukin-6 (IL-6) and interleukin-10 (IL-10) were measured by an enzyme lin ked immunosorbent assay. IL-6 and TNF-alpha levels elicited by the toxins w ere not reduced by night time levels of cortisol (5-10 mu g dl(-1)) levels. Day time levels of cortisol (10-20 mu g dl(-1)) significantly inhibited IL -6 production but not TNF-alpha in responses. Stress levels of cortisol (40 -80 mu g dl(-1)) significantly reduced all three cytokines earlier than the normal day time levels. The majority of the population tested had sufficie nt antibodies to reduce TNF-alpha and IL-6 responses elicited by TSST and S EC in the model system. In the age range in which most sudden unexpected no cturnal death cases occur (20-39 years), males had significantly lower leve ls of IgG to TSST compared with females. If these toxins play a role in pre cipitating the series of events leading to sudden unexpected nocturnal deat h, the higher levels of IgG to the toxins observed in females might explain partly the much higher prevalence of these deaths among men in this age ra nge. If inflammatory responses play a role in sudden unexpected nocturnal d eath, the inability of the night time levels of cortisol to control IL-6 an d TNF-alpha in the model system might reflect these interactions in vivo. T he methods developed for detection of the toxins in tissue samples and the quantitative IgG assays for anti-toxins can be applied to investigation of SUND victims to test the hypothesis that some of these deaths are precipita ted by pyrogenic staphylococcal toxins. (C) 1999 Published by Elsevier Scie nce B.V. All rights reserved.