Recovery of spleen cell natural killer activity by thyroid hormone treatment in old mice

The age-dependent changes in thyroid-hormone blood levels and the effects of in vivo and in vitro thyroid-hormone administration on both basal and lymphokine-induced spleen cell natural killer (NK) activities have been investigated in young and old Balb/c mice. Both thyroxine (T4) and triiodothyronine (T3) plasma levels decline progressively with increasing age of the mice, displaying in 25-month-old mice only 50 and 60% of the T4 and T3 blood levels, respectively, found in young mice. In vivo T4 administration to old mice causes a significant increment in endogenous NK activity (2.2-fold increase), which approaches the values observed in young animals, while it does not modify NK activity in young mice. The T4 injection in old mice does not induce changes in the lymphocyte sub-populations. When T4 is administered in vitro alone or in combination with interferon (IFN) and/or interleukin 2 (IL-2), no effect is observed either on basal activity or IL-2-induced cytotoxicity, whereas the IFN sensitivity of spleen cells from old mice is significantly recovered (4-fold increase). T4 is able to increase IFN-induced cytotoxicity even when administered in vitro simultaneously with IFN to the cytotoxic assay (1.5- and 2.7-fold increases in young and old mice, respectively). Under these conditions, IFN alone is not able to exert any boosting effect even at a young age. In vivo propylthiouracil (PTU) administration completely abrogates the IFN responsiveness of spleen cells in young mice. The interruption of the PTU treatment results in a recovery of IFN-inducible NK cytotoxicity. Taken together, our findings point out the important role of thyroid hormones in the modulation of NK cell activity and provide a new insight into the mechanisms by which the endocrine system is able to influence the expression of natural immunity.