Table 2. Allelic frequencies of )330 T fi G IL-2 SNP in cen- tenarians and controls from South-Center-Italy (percentages and frequencies per group is reported in parentheses).

ageing. Data are accumulating on the role that a high IL-2 production might play in immune- inflammatory mediated diseases. In humans, as reported by Solerte et al. (2000) high IL-2, as well as interferon-c and tumor necrosis factor- a, serum levels characterise subjects affected by Alzheimer’s disease. Furthermore, IL-2 increase has been associated with evolving atherosclerosis and coronary events in stable and unstable angi- na patients (Elkind et al. 2005; Methe et al. 2005). So the role of IL-2 in ageing might be more complex than that postulated as adaptive response rescue factor in immunosenescence (Lio et al. 2000; Candore et al. 2002; Pawelec et al. 2002). Immunosenescence, actually, may be considered an attempt to adapt response to the stressors of an aged immune system (Franceschi et al. 2005). A beneficial mechanism (i.e. geneti- cally determined IL-2 high production), devoted to the neutralization of dangerous/harmful agents early in life and in adulthood, turn to be detrimental late in life, in a period largely not foreseen by evolutionary strengths, and the reduction of IL-2 production, at least in part fa- voured by genetic background, or modification of cellular machinery of signal transduction might be a protective adaptation against age- related diseases that are ‘‘the price we pay’’ for a life-long active immune system (Caruso et al. 2005; Licastro et al. 2005).

IL2 )330 Alleles Centenarians Controls 336 (%) 428 (%) T 212 (63.1) 248 (57.9) G 124 (36.9) 180 (42.1)

No significant different distributions of IL-2 )330T/G alleles were observed among control and centenarian subjects.

Discussion

mediated immune response and defects in IL-2 mediated activation (e.g. for a deficit of c chain of Il-2 receptor) induce severe immune deficiency (Demoulin and Renauld 1998). An age-related decline in IL-2 production with associated effects on intracellular activation of nuclear transcrip- tion pathways involving reduction of ERK2 activity (Douziech et al. 2002) is considered a marker for immune senescence (Candore et al. 1992; Caruso et al. 1996; Rea et al. 1996; Pawelec et al. 2002). Recently a polymorphism (T/G), reported in the promoter region of IL-2 at ) the nucleotide position 330, (John et al. 1998), has been shown to influence IL-2 production and in vitro cytokine production in anti-D3/CD28- stimulated peripheral blood lymphocytes (Hoffman et al. 2001). G allele frequencies of ) IL-2 330 polymorphism in smaller samples of Caucasian populations across Europe have been documented as 30–40% in Germany, in Ireland and in North Italy (John et al. 1998; Rey- nard et al. 2000; Ross et al. 2003; Uboldi de Ca- pei et al. 2003) and about 35% was observed in our control population.

Acknowledgements

This work was supported by grants from the Italian Ministry of Education, University and Research to GC, DL, GCR, CC. Funds from Italian ministry of Health (Genetic and non- genetic factors of health in elderly) to CF, GP and GCR are also acknowledged. AC is a PhD student at Pathobiology PhD course (directed by C.C.) of Palermo University and this work is in partial fulfillment of the requirement for the PhD.

To date there is only an other study on IL-2 ) 330 G/T polymorphism frequency in aged peo- ple (but not in centenarians). The data, obtained comparing young and elderly Irish subjects (Ross et al. 2003), were in agreement with our present findings, showing a not significant in- crease of T allele frequencies in elderly. So pres- ent and previous reports seem to suggest that IL-2 low producer genotype is marginally, but not significantly, associated to longevity.

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