The lysosomotropic amines, chloroquine and hydroxychloroquine: a potentially novel therapy for graft-versus-host disease.

Abstract:

:We have recently shown that the lysosomotropic amine, chloroquine, can inhibit the development of graft-versus-host disease (GVHD) secondary to minor histocompatibility (MiHC) differences in mice. In addition, we have shown that both chloroquine and hydroxychloroquine can inhibit T cell responses in vitro to minor and major histocompatibility (MHC) antigens. We review the rationale for the use of lysosomotropic amines, whose primary mechanism of action appears to be inhibition of MHC class II antigen presentation, as therapy for GVHD in humans. Used in low concentrations, these agents appear to have no direct effect on T cells either in vitro or in vivo although they may have a direct effect at higher concentrations. The lysosomotropic amines, at low concentrations, in combination with the T cell-specific agent, cyclosporin A, synergistically suppresses the T cell response to MiHC and MHC in mouse and in human. We present the initial data from the human clinical trials using hydroxychloroquine. We hypothesize that the lysosomotropic amines may have unique beneficial effects on immune reconstitution following bone marrow transplantation. The lysosomotropic amines, hydroxychloroquine and chloroquine, represent agents with unique mechanisms of action that may be used to control GVHD in humans.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Schultz KR,Gilman AL

doi

10.3109/10428199709039008

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

201-10

issue

3-4

eissn

1042-8194

issn

1029-2403

journal_volume

24

pub_type

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