The role of antimalarial agents in the treatment of SLE and lupus nephritis

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that affects various organs. Lupus nephritis is one of the most common, and most important, serious manifestations of SLE. Antimalarial agents are part of the immunomodulatory regimen used to treat patients with SLE; however, their role in the treatment of patients with lupus nephritis in particular is less well recognized, especially by nephrologists. Not all antimalarial agents have been used in the treatment of lupus; this Review will focus on studies using chloroquine and hydroxychloroquine. In addition, this Review will briefly describe the history of antimalarial drug use in patients with SLE, the theorized mechanisms of action of the agents chloroquine and hydroxychloroquine, their efficacy in patients with SLE and those with lupus nephritis, their use in pregnancy, and potential adverse effects. The Review will also cover the latest recommendations regarding monitoring for hydroxychloroquine-associated or chloroquine-associated retinopathy. Overall, antimalarial drugs have numerous beneficial effects in patients with SLE and lupus nephritis, and have a good safety profile.

An SLE patient with prolactinoma and recurrent granulomatous mastitis successfully treated with hydroxychloroquine and bromocriptine

“…Hydroxychloroquine is known to alter lysosome stability, suppress antigen presentation, inhibit prostaglandin and cytokine synthesis, and influence both Toll-like receptor signaling and leukocyte activation. 9 Bromocriptine alone was not effective in our patient though its efficacy in treating the immunological disturbances in SLE has been documented.…”

A parasitic helminth-derived peptide that targets the macrophage lysosome is a novel therapeutic option for autoimmune disease

“…Given the dependence of many TLR functions upon lysosomal pH, modulators that control the luminal pH in macrophages represent valuable targets to treat autoimmune diseases and may expand therapeutic options. Testament to this, chloroquine (and its analogues) have been successfully used to treat autoimmune syndromes, such as SLE and RA (Martinson et al, 2010;Lee et al, 2011).…”

Glycogen Synthase Kinase-3 (GSK3) Inhibition Induces Prosurvival Autophagic Signals in Human Pancreatic Cancer Cells

“…In particular, given that we and others have suggested testing GSK3 inhibitors in the setting of PDAC patients (5,6,8,9,11,12,45,46), our results underscore the need to further explore the GSK3 downstream effectors to define better combination therapies. Concomitant GSK3 and autophagy inhibitors appear as an attractive new therapeutic option for PDAC patients given that such inhibitors, including lithium (47,48) and chloroquine (49), have been safely used in clinical settings for many years. However, before going down that road, inactivation of GSK3 combined with autophagy and/or TFEB inhibition will require detailed investigation in in vivo settings using, as an example, mouse models of PDAC.…”