title: 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).
abstract: There is evidence that inflammatory responses have been induced in the tissues and body fluids of many SIDS infants. We suggested that some of these deaths are due to uncontrolled inflammatory responses to infectious agents and possibly cigarette smoke. The majority of SIDS deaths occur during the 2-4 month age range when infants have decreasing levels of maternal antibodies to infectious agents. Most deaths occur during the early hours of the morning. Adults are more susceptible to inflammatory responses at night due to lower levels of cortisol associated with circadian rhythm patterns. Infants develop these patterns between the ages of 7 weeks and 4 months, at which time their night-time cortisol levels drop dramatically. The objective of this study was to use an in vitro model system to assess the effects of different cortisol levels on proinflammatory cytokine production 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 hours by a bioassay for tumour necrosis factor-alpha (TNF-alpha) and an enzyme linked immunosorbent assay (ELISA) for interleukin-6 (IL-6). Cortisol levels present in an infant at night after development of circadian rhythm (< or = 5 microg dl(-1)), did not significantly increase or decrease production of either TNF-alpha or IL-6. Concentrations of cortisol greater than 5 microg dl(-1) usually found in infants during the day or at night prior to the physiological change significantly decreased production of TNF-alpha at 12 hours and of IL-6 at 12 and 16 hours. Only cortisol levels greater than 5 microg dl(-1) significantly decreased production of the pro-inflammatory cytokines by human buffy coats stimulated with TSST-1. If the switch to the circadian rhythm pattern occurs in an infant when maternal antibodies are still present or after they have developed their own active immunity, the infant could neutralise common viruses, toxins or bacteria: however, if this switch occurs in an infant when antibody levels are low, this could be a window of vulnerability during which infants are at an increased risk of death if uncontrolled inflammatory responses are induced by infectious agents or their products.
authors.affiliation: Department of Medical Microbiology, University of Edinburgh, Scotland, UK. gordon@srv1.med.ed.ac.uk
authors.forename: A E
authors.initials: AE
authors.lastname: Gordon
authors.forename: O
authors.initials: O
authors.lastname: Al Madani
authors.forename: D M
authors.initials: DM
authors.lastname: Weir
authors.forename: A
authors.initials: A
authors.lastname: Busuttil
authors.forename: C
authors.initials: C
authors.lastname: Blackwell
mesh_terms: D001427:Bacterial Toxins; D002478:Cells, Cultured; D002940:Circadian Rhythm; D004768:Enterotoxins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D007223:Infant; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013398:Sudden Infant Death / Q000453:epidemiology / Q000276:immunology*; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D015850:Interleukin-6; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D006854:Hydrocortisone