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.
Moscovis
Sophia M
SM
School of Biomedical Sciences, Faculty of Health, Immunology and Microbiology, David Maddison Building, University of Newcastle, Newcastle, NSW 2300, Australia.
Gordon
Ann E
AE
Hall
Sharron T
ST
Gleeson
Maree
M
Scott
Rodney J
RJ
Roberts-Thomsom
June
J
Weir
Donald M
DM
Busuttil
Anthony
A
Blackwell
C Caroline
CC
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