Extracorporeal photopheresis reduces the number of mononuclear cells that produce pro-inflammatory cytokines, when tested ex-vivo.
Extracorporeal photopheresis (ECP) has been shown to be clinically effective in the treatment of many T cell-mediated conditions. ECP's mechanism of action includes the induction of apoptosis and the release of pro-inflammatory cytokines. Recently, we have observed early lymphoid apoptosis, detectable immediately post ECP. We were interested to determine what influence ECP has on pro-inflammatory cytokine secretion at this early pre-infusion stage. Samples from 6 cutaneous T cell lymphoma (CTCL) and 5 graft versus host disease (GvHD) patients were taken pre ECP and immediately post ECP, prior to re-infusion. Following separation, the PBMCs were added to a cell culture medium and stimulated with PMA, Ionomycin, and Brefeldin A for 6 hours. Using flow cytometry, intracellular cytokine expression of IFNgamma and TNFalpha was determined in the T cell population. The monocytes were evaluated for IL6, IFNgamma, IL12, and TNFalpha. For both patient groups, the number of IFNgamma-expressing T cells fell significantly at re-infusion, whilst both T cell- and monocyte-expressing TNFalpha levels were reduced at re-infusion. All other cytokines tested showed no significant change post ECP. For GvHD, pro-inflammatory cytokines have a pathological role. Their down-regulation may have a direct clinical benefit. However, the reduction in the number of IFNgamma- and TNFalpha-expressing mononuclear cells means, at this early stage, it is unlikely that these cytokines assist in the removal of the malignant Th2 cells present in CTCL.
Bladon
John
J
Department of Haematology, Rotherham General Hospital, South Yorkshire, United Kingdom. john.bladon@rothgen.nhs.uk
Taylor
Peter
P
D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators; D007371:Interferon-gamma / Q000032:analysis; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology / Q000473:pathology / Q000628:therapy; D017893:Photopheresis; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma