EFFECT OF L-ARGININE ON THYMIC FUNCTION - POSSIBLE ROLE OF L-ARGININE-NITRIC OXIDE (NO) PATHWAY

The thymus and in particular its epithelial component produces hormonal peptides which are required for differentiation of stem cells into mature T-cells. With advancing age, there occurs a progressive reduction of the plasma level of one of the best known thymic peptides, i.e. thymulin. In old mice, oral supplementation with arginine (9 x 10(-4) gr/day/mouse) for 1 month is able to induce a regrowth of the thymus and recovery of the reduced thymulin plasma level to the values observed in young animals. The direct immunological target of arginine seems to be the thymus gland. In fact, the transplantation of thymus from old arginine treated mice into young thymectomized recipients is able to restore thymulin plasma level in thymectomized recipients to nearly the same level as do thymuses from young mice. Furthermore, arginine supplementation young thymectomized recipients is unable to induce the reappearance of thymulin activity in the blood. With regard to the mechanism of action of arginine, two pathways may be suggested. The first one may be indirect and mediated by the secretagogue action of arginine on growth hormone. The second one, may rely on a direct action through the L-arginine:NO pathway. Lymphocyte-depleted thymic explants from young mice, when incubated in vitro with the NO-synthetase inhibiter L-NAME (6 mM), are, in fact, incapable of producing and realising thymulin in the supernatant. The in vitro addition of L-arg (60 mM) is able to recover such a production to the values observed in supernatants of control thymic cultures. The present findings offer the first evidence that also the thymic endocrine activity is modulated by L-arginine:NO pathway.