Immunosuppressive effects of chloroquine: potential effectiveness for treatment of post-transfusion graft-versus-host disease.
Post-transfusion graft-versus-host disease (PT-GVHD) is a fatal adverse effect of blood transfusion. In spite of its severity, there is no effective treatment at present for PT-GVHD. Previously, we reported that chloroquine (CH) inhibited the cytotoxicity of cytotoxic T-cell (CTL) clones and tumour necrosis factor beta (TNF beta) production by TNF beta-producing clones in vitro, both the clones being derived from peripheral blood lymphocytes (PBMCs) of PT-GVHD patients. To explore the possibility of utilizing CH for the treatment of PT-GVHD, we extended our investigation of the immunosuppressive effects of CH in vitro to PBMCs derived from healthy donors. Our results show that CH inhibits the mixed lymphocyte reaction (MLR) between allogeneic PBMCs, production of inflammatory cytokines such as TNF alpha, interleukin-1 beta (IL-1 beta) and interferon gamma (IFN gamma) in mixed lymphocyte culture and natural killer cell activity, and, further, reduces the number of alloreactive CTL precursors.
Nishimura
M
M
Department of Research, Japanese Red Cross, Tokyo, Japan.
Hidaka
N
N
Akaza
T
T
Tadokoro
K
K
Juji
T
T
D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D018655:Lymphocyte Count; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects; D065227:Transfusion Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007166:Immunosuppressive Agents; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002738:Chloroquine