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Human longevity seems to be directly correlated with optimal functioning of the immune system, suggesting that some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses, in particular cytokine gene polymorphisms. In fact, modification of cytokine network is a constant report in studies on age related modification of immune response. Moreover cytokine polymorphisms studies are indicating their involvement in the reshaping of cytokines network as an integral part of the scenario related to a successful ageing. A particular role might be attributed to the influence of cytokine polymorphisms on the efficiency of immune response against infectious diseases that have been the principal selection in oldest old. Here are reported data on the evaluation of the frequency of the functional polymorphisms at genes coding for TNF-alpha (-308G-->A) and IL-10 (-1082G-->A), analysed by ARMS-PCR, in a group of Sicilian patients affected by chronic lung tuberculosis (TBC) compared to that from a group of healthy individuals living in the same region. Data obtained demonstrated a reduction of -308GG TNF homozygous individuals in TBC affected subject group. In the same group a reduction of IL-10 -1082A/* carriers was found. Our results seem to suggest that multiple genetic traits may affect the capacity to cope with an infectious agents and this might predispose to an overt disease. Moreover these data are in agreement with previous reports suggesting that a balanced interaction among pro- and anti-inflammatory molecules it is a key point for conditioning the life span expectancy.

In the light of the key role played by interferon (IFN)-gamma in the control of tuberculosis, in the present paper we have evaluated the distribution of the functional +874T --> A IFN-gamma single nucleotide polymorphism (SNP) in Sicilian patients affected by tuberculosis. Our aim was to determine whether there is an association between the TT genotype, which has been suggested to be linked to an increased production of IFN-gamma, and resistance to chronic tuberculosis. DNA samples were obtained from 45 patients and 97 healthy controls. Polymorphism at +874 was identified using amplification refractory mutational system methodology. The +874T SNP was less frequent in patients than in controls (0.42 vs. 0.50) but the difference was not significant. The +874TT genotype, which has been suggested to be associated with high IFN-gamma production, was significantly decreased in the patients. Thus, resistance to chronic lung tuberculosis might be associated with a genetically determined high IFN-gamma production capacity. In conclusion, the present data add another piece of evidence to the complex puzzle of genetic and environmental factors involved in control of infectious diseases. Studies on cytokine gene polymorphisms may elucidate the complex network of trans-interactive genes influencing the type and strength of responses to environmental stressors and may help to identify the genetic factors that affect survival in humans.