Effects of nicotine on bacterial toxins associated with cot death.

Abstract

Toxins produced by staphylococci and enterobacteria isolated from the nasopharynx of cases of sudden infant death syndrome (SIDS) have a lethal effect when injected into chick embryos. If the toxins are progressively diluted the lethal effect disappears, but certain combinations of toxins show synergy so that if sublethal doses are mixed a highly lethal effect is produced. In this paper it is shown that nicotine at very low concentrations (less than that produced in man by 005 cigarettes) potentiates the lethal action of certain SIDS associated bacterial toxins and markedly potentiates the lethal action of synergistic combinations of bacterial toxins. These results could explain, at least in part, why parental smoking increases the risk of SIDS. They also provide further support for the common bacterial toxin hypothesis of cot death. (Arch Dis Child 1995; 73: 549- assessed by a chick embryo bioassay.8 Furthermore when tested in the same system certain combinations of toxins from the same infant show synergy with the result that a lethal effect is produced by very low toxin concentrations.9In this paper we present evidence that nicotine interacts with selected bacterial toxins potentiating the lethal effect of both single toxins and synergistic combinations. This suggests one possible explanation for the role of tobacco smoke in SIDS. MethodsBacterial isolates from the nasopharynx of SIDS cases had been obtained previously and stored at -70°C.10 To prepare toxins the bacteria were grown on a semipermeable membrane overlying a defined agar.8 In this system nutrients from the agar diffuse through the membrane to support surface growth but toxins secreted by the bacteria over a molecular weight of 12 000 are retained on the surface. The growth was then washed from the membrane and centrifuged and filtered to separate toxin secretions from live organisms. The crude toxin preparations were subsequently diluted to a standard optical density and tested for lethality by injection into the chorioallantoic vein of 11 day old embryonated chick eggs. Finally the eggs were incubated and tested for viability after 18 hours.In these experiments a Staphylococcus aureus and Kiebsiella pneumoniae isolated from one case of SIDS and S aureus and Escherichia coli isolated from a second case of SIDS were used. These pairs had been shown to cause lethal synergy in previous experiments. A series of doubling dilutions were prepared for each toxin preparation. Eleven eggs were injected with each dilution and the percentage lethality calculated. In each case a dilution was chosen which gave a low percentage kill; this was the neat concentration used in subsequent experiments.A solution of nicotine was also tested in the eggs in the same way as for the toxin preparations. A range of concentrations from 1 mg/ml to 7-8 pg/ml was tested. A concentration of 800 ng/ml (equivalent to 40 ng/egg)-was found to produce a lethal response in 22% of embryos. This was used as the neatsolution of nicotine.

The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position

“…There is both theoretical and experimental evidence in support of the hypothesis that toxins produced by bacteria that commonly colonise the nasopharynx have a pathogenic role in sudden infant death syndrome (SIDS) [1–7]. This idea, which is reviewed elsewhere in this issue, is consistent with the key epidemiological features of SIDS including the age distribution, the winter excess of cases and the association with prone sleeping and passive smoking.…”

Toxigenic bacteria and sudden infant death syndrome (SIDS): nasopharyngeal flora during the first year of life

“…In studies on exposure to cigarette smoke and respiratory infection in children, the strongest correlation is usually with the mother's smoking [42]. In model systems, both components of cigarette smoke and viral infection have been demonstrated to enhance the lethal effects of bacterial toxins [43] or the inflammatory responses to them [44–47].…”

The Mechanism of Dead-in-Bed Syndrome and Other Sudden Unexplained Nocturnal Deaths

“…Cases of SIDS occur due to either infection or synergy between exposures to cigarette smoke and infection [63][64][65]. Interestingly, sleep apnoea and defective arousal have been observed in the cases of near miss SIDS or victims of SIDS [66][67][68][69][70][71].…”