Selenium and the selenium-dependent glutathione peroxidase in rheumatoid arthritis

Selenium is an essential component in the two antioxidant enzymes glutathione peroxidase (GSH-Px) and phospholipid hydroperoxide glutathione peroxidase (PLGSH-Px). Free oxygen radicals are involved in the inflammatory process seen in rheumatoid arthritis (RA) and are generated mainly through the phagocytic activity of the polymorphonuclear leucocytes. Several experimental studies indicate that selenium is important to the functioning of the immune system and to the inflammatory process. A low selenium status among patients with RA has been reported from areas with both high and low natural selenium intake. The reduction in the serum level is approx. 10%. This reduction is related to the clinical disease activity in arthritis patients in both cross-sectional and longitudinal studies, and selenium concentrations have been found to fluctuate during the disease. Reduced selenium concentrations have been reported in red blood cells, too, and concentrations have been found to be slightly reduced in the polymorphonuclear leucocytes. Studies do not agree on the activity of GSH-Px among RA patients. Thus activity levels have been reported to range from low to high. Those studies that have focused on the subgroup of patients with high persistent disease activity have reported reduced GSH-Px activities in both serum, red blood cells and polymorphonuclear leucocytes. Selenium supplementation using organic selenium compounds in doses of around 250 microgram/day increases the selenium concentration in serum and red blood cells considerably. However, supplementation is not reflected in the selenium level in polymorphonuclear leucocytes from RA patients as opposed to healthy subjects, in whom the level of selenium in polymorphonuclear leucocytes increases. Selenium supplementation increased GSH-Px activity in serum, red blood cells and platelets from RA patients, but in the polymorphonuclear leucocytes the increase was not sufficient to reach the levels of the controls. This apparent lack of de novo synthesis of GSH-Px in polymorphonuclear leucocytes from RA patients may be explained by their inability to increase their selenium content in spite of high levels of available extracellular selenium. this may be in accordance with the lack of anti-arthritic effect of selenium supplementation in controlled clinical studies among RA patients. Several experimental studies have reported inhibition of GSH-Px by antirheumatic drugs, in particular gold. In addition, gold has been found to reduce selenium in rat plasma. These interactions can, however, be modified by increasing the amount of selenium in the feed. Among RA patients there is no clear evidence of an interaction between gold, selenium and GSH-Px.(ABSTRACT TRUNCATED AT 400 WORDS)