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Respiratory infections are particularly frequent in aged subjects and cause severe and often inauspicious complications) such as compromised cell-mediated immunity. Preliminary data suggest thymopentin treatment in a population of elderly subjects affected by relapses of bronchial disease. The effects of the therapy are adequately monitored controlling immunologic parameters.

The progressive decline of immune efficiency with advancing age has been investigated in Balb/c mice by measuring the spleen-cell responsiveness to both T- and B-mitogens and the capacity to form plaques after immunization with sheep erythrocytes. While the responsiveness to concanavalin A and lipopolysaccharide is not significantly decreased in old mice, the responsiveness to phytohaemagglutinin and the plaque-forming-cell capacity progressively diminish with advancing age. Such a functional decline has been correlated with the age-associated deterioration of the neurohormonal balance and particularly with the reduction of thyroxine blood levels. Reconstitution experiments carried out by treating animals of increasing ages with 15 daily injections of L-thyroxine have demonstrated that such a treatment is able to restore the age-related decline of immune efficiency, and that this recovery is associated with the reactivation of the thymic endocrine activity. These data are consistent with the idea that the neurohormonal balance may influence the immune efficiency and that its derangement with advancing age may represent one of the factors responsible for the aging of the immune system.

Congenital deficiencies of developmental hormones, such as growth hormone and thyroxine, are responsible for the thymus-dependent immunodeficiency disease observed in dwarf mice. Such an immunodeficiency state is associated with early aging phenomena. This fact suggests that lymphoid cells and primarily T-derived cells are involved in the control of aging processes.

The hypotesis of the thymus acting as biological clock for ageing is revisited. On the basis of data on the endocrine action of the gland, the age-dependent involution of the thymus is postulated to play a fundamental role on the deterioration of the immunological as well as the endocrine functions. Data either on beta-adrenergic responsiveness to Isoproterenol or on hormonal balance, tested on animal model with different degree of thymus efficiency, support this hypothesis.

Cell-mediated immune reactions, such as allogenic skin-graft rejection and PHA or MLC responses, and antibody synthesis against different antigens (sheep erythrocytes, Brucella antigen, bovine serum albumin) have been evaluated in rats suffering from experimentally-induced diabetes and in age-matched sham-treated controls. Cell-mediated immune reactions are strongly depressed diabetic rats. The cellularity of the thymus and of thymus-dependent areas and the number of peripheral blood lymphocytes is significantly reduced in pancreatectomized rats. Moreover, the immunological recovery from heavy cortisonization is also greatly impaired. Daily treatment with insulin may prevent these immunological alterations. By contrast, antibody responses in diabetic rats are not quantitatively altered in respect to either the number of antibody producing cells in the spleen or the circulating antibody titres. The discrepancy between the abnormality of cell-mediated immune reactions in diabetic rats and their physiological capacity to synthetize antibodies suggests that the sensitivity to an insulin-deprived environment is present only in a definite, although yet undefined, subpopulation of lymphoid cells rather than in the whole lymphoid system.

The age-dependent modifications of both basal and lymphokine-induced natural killer (NK) activity were analyzed in Balb/c inbred mice by measuring either the percentage of specific lytic activity in a 51 Cr release assay or the percentage of cells capable of binding the YAC-1 target cells. The basal lytic activity of spleen cells is low at birth, then it increases progressively and reaches a peak between 5 and 8 weeks of age and decreases thereafter, displaying in 25-month-old mice only 10% of the NK activity found in young mice. The number of spleen cells capable of binding target cells is higher at birth and then it declines progressively-old mice show about 40% of the binding capacity found in young mice. Significant in vitro NK activation is obtained in spleen cells from 25-, 50- and 750-day-old mice by incubation with interleukin-2 (IL-2) (1.8-fold increase in 25- and 50-day-old mice and 2.6-fold increase in 750-day-old mice) while no effect is obtained in 15-day-old mice. The responsiveness to in vitro stimulation with interferon (IFN) is not present in 15-day-old mice, however it appears in a defective way at the age of 25 days, and reaches its highest level in 50- and 180-day-old mice, (3.5- and 4.5-fold increase), still remaining present in 630-day-old mice, (two-fold increase) but not in 750-day-old mice. The in vivo injection with IFN increases the spleen cell NK activity of 25- and 50-day-old mice (3.6- and 2.3-fold increase respectively) but not of 15- and 750-day-old mice. The present data here confirm the existence of age-dependent variations of spleen cell NK activity and suggest a similar sequential timing of appearance/disappearance of IL-2 and IFN responsive spleen cells during ontogenetic development and aging respectively.