ANTI MALARIAL DRUGS
Anti malarial drugs have been used for the treatment of SLE and RA since the early 1900s. The precise mechanism of action remains uncertain, but they have been shown to inhibit cytokine (IL-1 and IL-6) production in vitro. The anti malarial pass freely through cell membranes at neutral pH, but in acidic environtments, such as endosomes, they become protonated and can no longer diffuse freely. This leads to concentration of the drug within endosomes and the collapse of endosomal pH gradients. It has been proposed that the inhibition of endosomal acidification interferes with antigen processing or, alternatively, that there is an effect on the interaction of microbial substances such as unmethylated CpG DNA or uridine-rich RNA with endosomal toll-like receptors (TLR9 and TLR7/TLR8, respectively). In addition to SLE and RA, anti malarials are used in the treatment of juvenile rheumathoid arthritis, Sjogren’s syndrome, and inflammatory myopathies.