Cortisol levels and control of inflammatory responses to toxic shock syndrome toxin-1 (TSST-1): the prevalence of night-time deaths in sudden infant death syndrome (SIDS)

There is evidence that inflammatory responses have been induced in the tiss ues and body fluids of many SIDS infants. We suggested that some of these d eaths are due to uncontrolled inflammatory responses to infectious agents a nd possibly cigarette smoke. The majority of SIDS deaths occur during the 2 -4 month age range when infants have decreasing levels of maternal antibodi es to infectious agents. Most deaths occur during the early hours of the mo rning. Adults are more susceptible to inflammatory responses at night due t o lower levels of cortisol associated with circadian rhythm patterns. Infan ts develop these patterns between the ages of 7 weeks and 4 months, at whic h time their night-time cortisol levels drop dramatically. The objective of this study was to use an in vitro model system to assess t he effects of different cortisol levels on proinflammatory cytokine product ion in response to the staphylococcal toxic shock syndrome toxin-1 (TSST-1) which has been identified in a significant number of SIDS infants. Levels of cortisol present in infants at night and during the day before and after the development of the circadian rhythm pattern were examined. Human buffy coats (n = 9) were stimulated with TSST-1 and responses assessed over 72 h ours by a bioassay for tumour necrosis factor-alpha (TNF-alpha) and an enzy me linked immunosorbent assay (ELISA) for interleukin-6 (IL-6). Cortisol le vels present in an infant at night after development of circadian rhythm (l ess than or equal to 5 mu g dl(-1)), did not significantly increase or decr ease production of either TNF-alpha or IL-6. Concentrations of cortisol gre ater than 5 mu g dl(-1) usually found in infants during the day or at night prior to the physiological change significantly decreased production of TN F-alpha at 12 hours and of IL-6 at 12 and 16 hours. Only cortisol levels greater than 5 mu g dl(-1) significantly decreased pro duction of the pro-inflammatory cytokines by human buffy coals stimulated w ith TSST-1. If the switch to the circadian rhythm pattern occurs in an infa nt when maternal antibodies are still present or after they have developed their own active immunity, the infant could neutralise common viruses, toxi ns or bacteria; however, if this switch occurs in an infant when antibody l evels are low, this could be a window of vulnerability during which infants are at an increased risk of death if uncontrolled inflammatory responses a re induced by infectious agents or their products. (C) 1999 Federation of E uropean Microbiological Societies, Published by Elsevier Science B.V. All r ights reserved.