John Bladon1, Peter C Taylor. 1. Department of Haematology, Rotherham General Hospital, South Yorkshire, UK. john.blandon@rothgen.nhs.uk
Abstract
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. CONCLUSION: ECP has both a direct and indirect immunosuppressive action, both of which may be beneficial in the treatment of GvHD.
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 GvHDpatients, 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. CONCLUSION: ECP has both a direct and indirect immunosuppressive action, both of which may be beneficial in the treatment of GvHD.
Authors: A Legitimo; R Consolini; A Failli; S Fabiano; W Bencivelli; F Scatena; F Mosca Journal: Clin Exp Immunol Date: 2007-03-26 Impact factor: 4.330