Plasma thiols, copper and rheumatoid arthritis

A means by which methotrexate diminishes the overproduction of leukotriene B4 by neutrophils from rheumatoid arthritic patients is described. It is postulated that neutrophil intracellular reduced glutathione is decreased by increased cellular copper, which results in leukotriene B4 overproduction. In the arthritic patient it is proposed that there is an inappropriate amount of a copper donor form of ceruloplasmin which contains a reduced copper that was formed during ceruloplasmin's oxidation of plasma cysteine. Oxidation of increased amounts of plasma homocysteine, present during methotrexate administration, restores ceruloplasmin's redox state leading to decreased copper transport into cells.