Journal of Immunology 2015-03-15

Extracorporeal photopheresis promotes IL-1β production.

Erhan Yakut, Christopher Jakobs, Adriana Peric, Gabriela Michel, Nelli Baal, Gregor Bein, Bernhard Brüne, Veit Hornung, Holger Hackstein

Index: J. Immunol. 194(6) , 2569-77, (2015)

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Abstract

Extracorporeal photopheresis (ECP) is a widely used clinical cell-based therapy exhibiting efficacy in heterogenous immune-mediated diseases such as cutaneous T cell lymphoma, graft-versus-host disease, and organ allograft rejection. Despite its documented efficacy in cancer immunotherapy, little is known regarding the induction of immunostimulatory mediators by ECP. In this article, we show that ECP promotes marked release of the prototypic immunostimulatory cytokine IL-1β. ECP primes IL-1β production and activates IL-1β maturation and release in the context of caspase-1 activation in monocytes and myeloid dendritic cells. Of interest, IL-1β maturation by ECP was fully intact in murine cells deficient in caspase-1, suggesting the predominance of an inflammasome-independent pathway for ECP-dependent IL-1β maturation. Clinically, patient analysis revealed significantly increased IL-1β production in stimulated leukapheresis concentrates and peripheral blood samples after ECP. Collectively, these results provide evidence for promotion of IL-1β production by ECP and offer new insight into the immunostimulatory capacity of ECP. Copyright © 2015 by The American Association of Immunologists, Inc.