title: Increased circulating Interleukin-18 levels in centenarians with no signs of vascular disease: another paradox of longevity?
abstract: Interleukin (IL)-18 is highly expressed in macrophages from human atherosclerotic plaques, suggesting its involvement in ischemic syndromes. We evaluated IL-18 and IL-18 binding protein (BP) in healthy centenarians, as longevity is characterized by a reduced incidence of ischemic events. For comparison, patients with chronic ischemic syndromes (CIS) were evaluated. Serum IL-18 and IL-18BP levels were measured by non-cross-reacting ELISA in 16 healthy centenarians and in two age-control populations, each of 18 healthy individuals aged 55.9+/-1.43 and 74.3+/-1.35, respectively, as well as in 23 CIS patients, and another cohort of 23 healthy subjects that were age- and sex-matched with CIS patients. Centenarians displayed significantly higher total IL-18 serum levels compared to each control group. Elevated IL-18 levels were also present in CIS patients. However, centenarians had a significant higher level of IL-18BP compared to the cohort of 23 controls (P=0.0014), and compared to CIS patients (P=0.043); as a result centenarians exhibited a lower level of free IL-18 than CIS patients. The present results indicate that quenching of IL-18 by IL-18BP may explain the apparent paradox of elevated serum IL-18 with no vascular signs in centenarians.
authors.affiliation: Department of Human Pathology, University of Messina, 98125, Messina, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Gangemi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Basile
authors.forename: Rosaria Alba
authors.initials: RA
authors.lastname: Merendino
authors.forename: Paola Lucia
authors.initials: PL
authors.lastname: Minciullo
authors.forename: Daniela
authors.initials: D
authors.lastname: Novick
authors.forename: Menachem
authors.initials: M
authors.lastname: Rubinstein
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Claudia
authors.initials: C
authors.lastname: Lo Balbo
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Stefania
authors.initials: S
authors.lastname: Basili
authors.forename: Etrusca
authors.initials: E
authors.lastname: D' Urbano
authors.forename: Giovanni
authors.initials: G
authors.lastname: Daví
authors.forename: Vittorio
authors.initials: V
authors.lastname: Nicita-Mauro
authors.forename: Mario
authors.initials: M
authors.lastname: Romano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000276:immunology; D001161:Arteriosclerosis / Q000097:blood* / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18 / Q000097:blood*; D008136:Longevity / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C118370:interleukin-18 binding protein