{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T02:36:31Z","timestamp":1785206191755,"version":"3.55.0"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,5,10]],"date-time":"2006-05-10T00:00:00Z","timestamp":1147219200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract:\u2002<\/jats:sc><\/jats:bold>  <jats:bold>The total burden of infection at various sites may affect the progression of atherosclerosis, the risk being modulated by host genotype. The role of lipopolysaccaride receptor TLR4 is paradigmatic. It initiates the innate immune response against gram\u2010negative bacteria; and TLR4 polymorphisms, as ASP299GLY, suggested to attenuate receptor signaling, have been described. We demonstrated that TLR4 ASP299GLY polymorphism shows a significantly lower frequency in patients affected by myocardial infarction compared to controls, whereas centenarians show a higher frequency. Thus, people genetically predisposed to developing weak inflammatory activity, seem to have fewer chances of developing cardiovascular diseases (CVD) and, subsequently, live longer if they do not become affected by serious infectious diseases. These results are in agreement with our other data demonstrating how genetic background may exert the opposite effect with respect to inflammatory components in CVD and longevity. In the present report, to validate this hypothesis, the levels of interleukin (IL)\u20106, a pro\u2010inflammatory cytokine involved in atherosclerosis and longevity, were determined by an enzyme\u2010linked immuno\u2010sorbent assay (ELISA) in supernatants from a whole blood assay after stimulation with subliminal doses of lipopolysaccaride (LPS) from <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E. coli<\/jats:italic>). The samples, genotyped for the ASP299GLY polymorphism, were challenged with LPS for 4, 24, and 48 h. What we found was that Il\u20106 values were significantly lower in carriers bearing TLR4 mutation. Therefore, the pathogen burden, by interacting with host genotype, determines the type and intensity of the immune\u2010inflammatory responses accountable for pro\u2010inflammatory status, CVD, and unsuccessful aging. On the other hand, our present data seem to explain the inconclusive results obtained in case\u2013control studies taking into account the role of functional IL\u20106 polymorphisms in successful and unsuccessful aging. In fact, IL6 levels seem to depend, in addition, on IL\u20106 polymorphisms and on innate immunity gene polymorphisms as well.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1354.037","type":"journal-article","created":{"date-parts":[[2006,6,27]],"date-time":"2006-06-27T16:32:09Z","timestamp":1151425929000},"page":"282-287","source":"Crossref","is-referenced-by-count":59,"title":["Inflammation, Longevity, and Cardiovascular Diseases"],"prefix":"10.1111","volume":"1067","author":[{"given":"GIUSEPPINA","family":"CANDORE","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ALESSANDRA","family":"AQUINO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CARMELA RITA","family":"BALISTRERI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MATTEO","family":"BULATI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DANIELE","family":"DI CARLO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARIA PAOLA","family":"GRIMALDI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FLORINDA","family":"LIST\u00cc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"VALENTINA","family":"ORLANDO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SONYA","family":"VASTO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARCO","family":"CARUSO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GIUSEPPINA","family":"COLONNA\u2010ROMANO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DOMENICO","family":"LIO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CALOGERO","family":"CARUSO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,5,10]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2002.001297"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(05)01308-3"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2006.9.143"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.19.2339"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364147"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.019885"},{"key":"e_1_2_5_8_2","unstructured":"Caruso C.et al.2004.Genetic background of centenarians may be protective against cardiovascular disease. Immunology 2004 Proceedings of the International Immunology Congress Canada. pp.29\u201334.Monduzzi. Bologna Italy ."},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.307.5707.208"},{"key":"e_1_2_5_10_2","volume-title":"Cytokine Gene Polymorphisms in Multifactorial Conditions","author":"Candore G.","year":"2006"},{"key":"e_1_2_5_11_2","volume-title":"Cytokine Gene Polymorphisms in Multifactorial Conditions","author":"Rea I.M.","year":"2006"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2003.10.001"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000147534.69062.dc"},{"key":"e_1_2_5_14_2","article-title":"Toll\u2010like receptor 4 D299G polymorphism predicts lower risk of coronary artery diseases and diabetes","volume":"108","author":"Kolek M.J.","year":"2003","journal-title":"Circulation"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2004.08.028"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4933-2-8"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1354.037","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1354.037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T19:09:44Z","timestamp":1695668984000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1354.037"}},"subtitle":["Role of Polymorphisms of TLR4"],"short-title":[],"issued":{"date-parts":[[2006,5]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,5]]}},"alternative-id":["10.1196\/annals.1354.037"],"URL":"https:\/\/doi.org\/10.1196\/annals.1354.037","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,5]]}}}