Anti-malarial drugs: possible mechanisms of action in autoimmune disease and prospects for drug development

Lupus. 1996 Jun;5 Suppl 1:S4-10.

Abstract

A wide variety of mechanisms of anti-rheumatic action have been proposed for anti-malarial agents. The molecular actions of chloroquine have been most thoroughly studied in vitro and in vivo, but it is likely that hydroxychloroquine works by a similar mechanism. Both agents are weak diprotic bases that can pass through the lipid cell membrane and preferentially concentrate in acidic cyto-plasmic vesicles. The resulting slight elevation of pH within these vesicles in macrophages or other antigen-presenting cells may influence the immune response to autoantigens. We hypothesize that anti-malarial agents influence the association of autoantigenic peptides with class II MHC molecules in the compartment for peptide loading and/or the subsequent processing and transport of the peptide-MHC complex to the cell membrane. This model of anti-malarial action provides a method to test additional drugs for their ability to modulate the immune response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antigen Presentation / drug effects
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Autoantigens / metabolism
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Chloroquine / chemistry
  • Chloroquine / pharmacology
  • Drug Design
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Hydroxychloroquine / chemistry
  • Hydroxychloroquine / pharmacology
  • Peptides / immunology
  • Peptides / metabolism
  • Rheumatic Diseases / drug therapy
  • Rheumatic Diseases / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Antimalarials
  • Autoantigens
  • Histocompatibility Antigens Class II
  • Peptides
  • Hydroxychloroquine
  • Chloroquine