Polymorphism of age-related changes in interleukin (IL) production: differential changes of T helper subpopulations, synthesizing IL 2, IL 3 and IL 4.

Inbred mice were examined for strain differences in age-associated changes in the capacity to synthesize interleukin (IL), i.e. IL 2, IL 3 and IL 4 after stimulation with phorbol myristate acetate (PMA) and calcium ionophore (A23187). Production of IL 2 remains constant in A/J, DBA/1 and DBA/2 mice and decreases with age in one of the strains examined (C57BL/6J). Strain differences in age-associated change of synthesis did not show the relation between youthful synthetic capacity and magnitude of later decrease ("economic correction") which is observed in several other systems. This difference between different types of polymorphisms is attributed to an age-associated defect in intrinsic capacity to synthesize IL 2 which may occur in only one of the tested strains, C57BL/6J. In contrast to IL 2 production, the quantities of IL 3 and IL 4 increase progressively, with advancing age, in mice of the three strains tested. T cells from old mice contain a greater frequency of cells producing IL 3, than do those of young mice. In addition, synthesis of IL 3 is induced at a relatively lower concentration of PMA in cells from old animals and this may be a consequence of different signal requirements of the two subsets of the T helper cells, but also a change in intrinsic properties of these cells. Since IL 3 and IL 4 production, but not IL 2 production, increases with age, it is reasonable to conclude that this reflects an expansion of a T helper cell population which secretes IL 3 and IL 4, but not IL 2, presumably TH2.