Chloroquine prevents T lymphocyte suppression induced by anthrax lethal toxin.
Lysosomal processing of lethal toxin (LTX) is a key event in the pathogenesis of anthrax. This study investigated the ability of chloroquine (CQ) to interfere with this processing and thereby to reduce suppression of T lymphocytes. T lymphocytes isolated from blood were activated, by cross-linking of CD3, in both the absence and presence of LTX and CQ and then were assayed by flow cytometry and immunoblotting. LTX was found to disrupt intracellular signaling, and it down-regulated T lymphocyte function. CQ significantly reduced the harmful effects of LTX and protected the activation and cytokine production of T lymphocytes. This effect may indicate a promising strategy in the treatment of anthrax.
Hirsh
Mark I
MI
Laboratory for Shock and Trauma Research, Rambam Medical Center, Bruce Rappaport Faculty of Medicine, Technion, 31096 Haifa, Israel. hirsh@tx.technion.ac.il
Cohen
Victoria
V
D000328:Adult; D000942:Antigens, Bacterial / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000942:Antigens, Bacterial; D000962:Antimalarials; D001427:Bacterial Toxins; D014409:Tumor Necrosis Factor-alpha; C030325:anthrax toxin; D016753:Interleukin-10; D002738:Chloroquine