Interleukin-1 polymorphisms and graft-vs-host disease

Abstract

Graft-vs-host disease (GVHD) remains a key limiting factor in the success of hematopoietic stem cell transplantation (HSCT). One of the key cytokines known to have a role in the pathogenesis of GVHD is interleukin-1 (IL-1). The IL-1 gene family consists of 10 members, of which 3 genes encode for the proteins IL-1a, IL-1ss and IL-1Ra (IL-1 receptor antagonist). Polymorphisms in these genes have been associated with variability in the production of the respective cytokines and have been implicated in patient susceptibility to inflammatory diseases, including GVHD. A number of reports have detailed genetic associations between members of the IL-1 gene family and HSCT outcomes. Despite these encouraging reports, a simple exploitation of these findings is probably naive. Differences in transplant practice between centers and within centers over time mean that directly comparable studies are rare. This combined with the complexity of IL-1-related transplant biology means that our understanding of this topic remains limited. This review details the current state of knowledge of IL-1 genetics and transplantation and discusses these issues in the context of the changing practice of transplantation.

Prehematopoietic Stem Cell Transplantation Tear Cytokines as Potential Susceptibility Biomarkers for Ocular Chronic Graft-Versus-Host Disease

“…58 Moreover, polymorphisms in IL-1 family genes have been associated with variability in the production of the respective cytokines and have been implicated in patient susceptibility to GVHD. 59 The explanation for this apparent protective role could be related to a regulatory effect during IL-1-related inflammatory cascade.…”

Interleukin-1 gene complex polymorphisms in systemic sclerosis patients with severe restrictive lung physiology

“…The interleukin-1 family is composed of several members: IL-1␣ and IL-1␤ are two different but related agonist polypeptide cytokines, which act by binding to one of the two IL-1 receptors (IL-1R) and whose action is counteracted by their natural antagonist, the IL-1 receptor antagonist (IL-1Ra) [10]. All members of IL-1 gene complex are located on chromosome 2q13-21 [11]; several polymorphisms were identified in this region, some of which can modify the function or the amount of IL-1 [12][13][14][15] and are claimed to be relevant under many pathological conditions, including chronic inflammatory and autoimmune diseases [16,17], graft-versus-host disease [18], pneumoconiosis, and other interstitial lung diseases [7,19].…”

Advances in the understanding of acute graft‐versus‐host disease

“…In these studies, target organ damage was prevented by the neutralisation of IL‐1 and TNF. IL‐1 is a critical promoter of pro‐inflammatory immune responses, and polymorphisms in the genes encoding the 10 members of the IL‐1 family have important effects on the incidence and severity of experimental GVHD (Cullup & Stark, 2005; Dickinson & Charron, 2005). TNF has central roles at several stages of GVHD, including the enhancement of APC maturation, promotion of cellular trafficking, enhancement of T‐cell responses (Hill et al , 2000) and the direct induction of tissue injury (Laster et al , 1988).…”

“…Although miHA contribute to alloreactivity and GVHD, genes controlling inflammatory processes, such as cytokines, chemokines and their receptors, can modulate GVHD. Gene polymorphisms affecting IL‐1 (Cullup & Stark, 2005), IL‐6 (Fishman et al , 1998), IL‐10 (Cooke & Ferrara, 2003; Lin et al , 2003), TNF (Cavet et al , 1999), transforming growth factor β (TGF‐ β ) (Hattori et al , 2002) and IFN‐ γ (Cayabyab et al , 1994) have all been implicated in the incidence and severity of GVHD, both in experimental models and immuno‐genetic analysis of retrospective clinical data [recently reviewed (Dickinson & Charron, 2005)].…”