Lymphocytes treated by extracorporeal photopheresis can down-regulate cytokine production in untreated monocytes.
BACKGROUND
Pro-inflammatory cytokines are actively involved in graft-versus host-disease (GvHD) aetiology. Treatment of GvHD, using extracorporeal photopheresis (ECP), has demonstrated clinical efficacy. ECP rapidly reduces the number of T cells that produce tumour necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma) and interleukin (IL)2. ECP-treated cells are re-infused immediately after completion of treatment. This study attempted to determine the influence that ECP-treated cells would have on untreated cells following re-infusion.


METHODS
Heparinized samples were taken from 10 chronic GvHD patients, pre-ECP and immediately prior to re-infusion (post-ECP). Lymphocytes and monocytes were isolated using magnetic separation. The post-ECP lymphocytes were mixed with pre-ECP monocytes, while the post-ECP monocytes and pre-ECP lymphocytes were combined. After suitable stimulation, the T cells were tested for intracellular TNFalpha, IFNgamma and IL2, while the monocytes were evaluated for TNFalpha, IL1alpha, IL1beta, IL6 and IL8.


RESULTS
Although cytokine secretion is decreased in T cells exposed to ECP, pre-ECP T cells were unaffected by post-ECP monocytes. Post-ECP monocytes demonstrated a reduction in cytokine secretion. Furthermore, untreated monocytes down-regulated cytokine production following exposure to ECP-treated lymphocytes.


CONCLUSIONS
ECP has both a direct and indirect immunosuppressive action, both of which may be beneficial in the treatment of GvHD.
Bladon
John
J
Department of Haematology, Rotherham General Hospital, South Yorkshire, UK. john.blandon@rothgen.nhs.uk
Taylor
Peter C
PC
D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D019337:Hematologic Neoplasms / Q000150:complications / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D017893:Photopheresis / Q000379:methods
D016207:Cytokines