THE EFFECT OF HYDROXYCHLOROQUINE ON ALLOREACTIVITY AND ITS POTENTIAL USE FOR GRAFT-VERSUS-HOST DISEASE

Hydroxychloroquine (HCQ) interferes with antigen processing and with r eceptor loading and recycling by raising the pH of lysosomes and endos omes. HCQ thus inhibits MHC class II-restricted antigen presentation b y blocking the binding of peptides to MHC molecules. Additionally, HCQ has been shown to diminish the release of several cytokines. In light of these mechanisms of action, we felt that HCQ might be useful in th e bone marrow transplant setting and therefore investigated its effect on alloreactivity in vitro. We have demonstrated that HCQ causes a do se-dependent reduction of the cytotoxicity, proliferation, and TNF alp ha production resulting from allorecognition in mixed lymphocyte cultu re (MLC). HCQ does not mediate its effect solely through antigen proce ssing and presentation and other early events since addition of HCQ as late as 120 h after the initiation of the MLC still has a suppressive effect on cytotoxicity. HCQ also inhibits the cytotoxicity of previou sly primed effecters. These results support an effect of HCQ on termin al mechanisms of cytotoxicity that have not been previously reported. HCQ's ability to reduce the cytotoxicity, proliferation, and TNF alpha production resulting from allorecognition suggests that it may be use ful in the prevention and treatment of graft-versus-host disease (GVHD ).