Lymphocytes treated by extracorporeal photopheresis can down-regulate cytokine production in untreated monocytes
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 α (TNFα), interferon (IFN) 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 TNFα, IFN and IL2, while the monocytes were evaluated for TNFα, IL1α, IL1, 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.
Document Type: Research Article
Publication date: December 1, 2005