Interleukin 1-beta responses to bacterial toxins and sudden infant death syndrome.
We tested the hypothesis that significantly higher IL-1beta responses to toxic shock syndrome toxin (TSST) noted for parents of sudden infant death syndrome (SIDS) infants might be due in part to genetic factors such as the IL-1beta (C-511T) and IL-1RN (T+2018C) single nucleotide polymorphisms (SNP). The first objective was to assess the distribution of these polymorphisms among SIDS infants, parents of SIDS infants and controls, and two ethnic groups: Aboriginal Australians who have a high incidence of SIDS; and Bangladeshis who in Britain have a low incidence of SIDS compared with Europeans. The second objective was to assess IL-1beta responses to endotoxin and toxic shock syndrome toxin (TSST) from leukocytes of smokers and non-smokers in relation to these polymorphisms. There were major differences in the distributions of the IL-1beta (C-511T) SNP between Europeans and Bangladeshis (p=0.00) and between Europeans and Aboriginal Australians (p=0.00); however, they were similar for the Bangladeshi and Aboriginal Australian subjects. The allele frequency distribution of the IL-1RN (T+2018C) SNP for the Aboriginal Australians was statistically different from the European group (p=0.00), but it was not different from the Bangladeshi group (p=0.09). Compared with controls of European origin, there were no significant differences in the distribution of these polymorphisms among SIDS infants or parents of SIDS infants. For the IL-1beta (C-511T) SNP, the highest IL-1beta responses to endotoxin were obtained with leukocytes of non-smokers with the heterozygous CT genotype. Smokers had significantly lower levels of IL-1beta in response to endotoxin (p=0.01) and these differences were significant for donors with the wild type CC (p=0.00) and CT (p=0.03) genotypes. Similar patterns were observed for IL-1beta responses to TSST, but the differences were not significant. For the IL-1RN (T+2018C) SNP, the highest IL-1beta responses to endotoxin were obtained with leukocytes from non-smoker donors with the wildtype TT genotype and significantly lower responses were found with leukocytes from donors with the TC genotype (p=0.02). The responses of smokers were lower but the differences were significant only for donors with the TT genotype (p=0.00). Similar patterns were observed for IL-1beta responses to TSST, but the differences were not significant. IL-1beta responses to both endotoxin and TSST were increased for the small number of smokers with the TT genotype of the IL-1beta (C-511T) SNP. The TT genotype of the IL-1beta (C-511T) was found predominantly among Aboriginal Australian and Bangladeshi individuals but only a small proportion of Europeans. Smokers with the AA genotype of the IL-10 (G-1082A) SNP which is found predominantly among these two groups had significantly lower levels of IL-10 responses. If cigarette smoke enhances pro-inflammatory responses and reduces anti-inflammatory responses in individuals with these genotypes, this might partly explain the increased susceptibility of Aboriginal Australian infants to infections and SIDS.
School of Biomedical Sciences, Faculty of Health, Immunology and Microbiology, David Maddison Building, University of Newcastle, Newcastle, NSW 2300, Australia.
Sophia M
SM
Moscovis
Ann E
AE
Gordon
Sharron T
ST
Hall
Maree
M
Gleeson
Rodney J
RJ
Scott
June
J
Roberts-Thomsom
Donald M
DM
Weir
Anthony
A
Busuttil
C Caroline
CC
Blackwell
D001427:Bacterial Toxins / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups; D017472:Receptors, Interleukin-1 / Q000235:genetics; D012907:Smoking; D013398:Sudden Infant Death / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D018089:Superantigens / Q000276:immunology
D001427:Bacterial Toxins; D004768:Enterotoxins; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal