Chapter 17 - Cytokines in GVHD and GVL

Abstract

Cytokines are critical drivers of both pathology (i.e., graft-versus-host disease [GVHD]) and protection (i.e., graft-versus-leukemia [GVL]) after hematopoietic stem cell transplantation, and an understanding of their biology is important for understanding both the pathophysiology of disease, together with existing and future treatment modalities. The critical cytokines promoting pathology in GVHD are interferon-gamma, tumor necrosis factor, and interleukin (IL)-6, as these have involvement in the gastrointestinal tract, skin and lung, though paradoxically interferon-gamma signaling provides protection from lung GVHD/idiopathic pneumonia syndrome. Many other cytokines are important in the overall inflammatory cytokine storm that is characteristic of acute GVHD, including the largely “proinflammatory” molecules IL-1, IL-2, IL-12, IL-17, IL-21, IL-33, and the regulatory/protective molecules IL-10, IL-22, and TGF-β. This chapter provides an overview of cytokine signaling in GVHD and GVL and highlights the preclinical and clinical evidence for current cytokine-associated paradigms in GVHD pathophysiology.