Age-related changes in arachidonic acid metabolism of normal, leukemic and autoimmune strain mice

Abstract

Spleen synthesis of prostaglandins (PGs) and thromboxane (Tx) was examined as a function of age for autoimmune, leukemic and normal mouse strains. Prostaglandin and thromboxane production from 14C-arachidonic acid was assessed from 20 minute synthesis by tissue homogenates. Values for young animals, six to 10 weeks of age, were compared to those for eight-to 12-month-old mice, except in the cases of the early autoimmune strain BXSB male and MRL/Ipr mice which were examined at five to seven months of age. Total eicosanoid synthesis, as well as PGF2α , PGE2, and PGD2 production showed, in general, a pattern of increase with age in nonautoimmune strain BALB/c, C57BI/6 and female BXSB mice. In contrast, PGE2 and PGF2α synthesis decreased in the autoimmune MRL/Ipr and male BXSB models and in the nonautoimmune, but lymphoma-developing AKR strain. The late autoimmune MRL/++ strain showed decreased PGE2 but no change in PGF2α with age. Age-related PGE2 and PGF2α changes were minimal in the nonautoimmune DBA/2 and in the late autoimmune PN strains. Thromboxane B2 appeared to be conserved in all strains studied. The results suggest that diminished spleen PG production with age is linked to development of autoantibodies and lymphoproliferative disorders. Further studies are necessary to establish whether decreased synthesis of immunoregulatory PGs plays a causal role in disease development or arises as a consequence of disease.