Calpain activity and expression are increased in splenic inflammatory cells associated with experimental allergic encephalomyelitis.

Since calcium-activated neutral proteinase (calpain) activity and expression are significantly increased in activated glial/inflammatory cells in the central nervous system of animals with autoimmune demyelinating diseases, this enzyme may also play a role in peripheral organ systems in these diseases. In this study, the activity and expression of calpain and the endogenous inhibitor, calpastatin, were evaluated at transcriptional and translational levels in spleens of Lewis rats with acute experimental allergic encephalomyelitis (EAE) prior to the onset of clinical symptoms. Calpain activity and translational expression were increased by 475.5% and 44.3% respectively, on day 4 post-induction in adjuvant controls and animals with EAE. These levels remained elevated compared to normal controls on days 8 and 12. Calpastatin translational expression was similarly increased at these time points although transcriptional expression was not significantly altered at any time following induction of EAE. Likewise, transcriptional expression of mu-calpain was unchanged following induction, while small increases in m-calpain transcriptional expression were observed on days 2 and 8. Most calpain expression was observed in activated splenic macrophages at day 8 post-induction even though activated T cells were also calpain positive. In spinal cords of animals with EAE, calpain expression was significantly increased in rats with severe disease compared to those exhibiting only mild symptoms at day 12 post-induction. Thus, prior to symptomatic EAE, increased calpain activity and expression in peripheral lymphoid organs may play an important role in T cell migration and subsequent disease progression.

Immunomodulating properties of dimethylglycine in humans.

Dimethylglycine (DMG), a tertiary amino acid, has had wide acceptance as a nonfuel nutrient; presumably it enhances oxygen utilization by tissue and complexes free radicals. Its potential as an immunoadjuvant has also been suggested by a study of an analog of DMG, calcium pangamate. A double-blind study in 20 human volunteers showed a fourfold increase in antibody response to pneumococcal vaccine in those receiving DMG orally as compared with controls (P less than 0.01). Production of leukocyte inhibitory factor in response to concanavalin A was similar in the two groups, but those taking DMG tablets had a significantly highr mean response of leukocyte inhibition factor to streptokinase-streptodornase (P less than 0.001). The in vitro responses of lymphocytes from patients with diabetes and those with sickle cell disease to phytohemagglutinin, convanavalin A, and pokeweed mitogen were increased almost threefold after addition of DMA. These results suggest that DMG enhances both humoral and cell-mediated immune responses in humans.