Effect of zinc supplementation on plasma IL-6 and MCP-1 production and NK cell function in healthy elderly: interactive influence of +647 MT1a and -174 IL-6 polymorphic alleles.
Pro-inflammatory cytokine response and NK activity are controlled by the availability of zinc ion, whose intra-cellular transport is regulated by metallothioneins. In order to closely examine the importance of circulating zinc in the modulation of immune response during ageing, in the balance of Th2/Th1 equilibrium and finally in the reversibility of systemic low grade inflammation, we evaluated the changes occurring in plasma IL-6 and MCP-1 concentrations and NK lytic activity in a healthy low grade inflamed elderly population, following zinc-aspartate supplementation. In addition, we aimed to highlight the potential interaction among circulating zinc increments, changes in immunological parameters and +647 MT1a and -174 IL-6 polymorphic alleles. Thirty-nine healthy individuals (60-83 years) from the ZINCAGE cohort (previously typed for +647 MT1a and -174 IL-6 polymorphisms) were supplied with zinc-aspartate. Blood samples collected before and after supplementation underwent basal laboratory determinations (circulating zinc, albumin and C-reactive protein) and immunological studies (plasma IL-6 and MCP-1 and NK lytic activity). Zinc supplementation in subjects with low or borderline-normal circulating zinc increased the concentration of this ion and modulated plasmatic IL-6 and MCP-1 as well as NK lytic activity. An interactive effect of polymorphic alleles of MT1a and IL-6 genes on zinc, IL-6, MCP-1 and NK activity was evidenced following supplementation, indicating the genetic background as one of the determinants for identifying groups of subjects that can take advantage of therapeutic intervention.
Mariani
Erminia
E
Istituto di Ricerca Codivilla-Putti, IOR, Via di Barbiano 1/10, 40136 Bologna, Italy. marianie@alma.unibo.it
Neri
Simona
S
Cattini
Luca
L
Mocchegiani
Eugenio
E
Malavolta
Marco
M
Dedoussis
George V
GV
Kanoni
Stavroula
S
Rink
Lothar
L
Jajte
Jolanta
J
Facchini
Andrea
A
D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000187:drug effects*; D008297:Male; D008668:Metallothionein / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012709:Serum Albumin / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects; D014131:Trace Elements / Q000008:administration & dosage / Q000494:pharmacology*; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; C530099:MT1A protein, human; D012709:Serum Albumin; D014131:Trace Elements; D002097:C-Reactive Protein; D008668:Metallothionein; D015032:Zinc