Interleukin-27 as a Novel Therapy for Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is an inflammatory disorder of the intestine that affects an estimated 329 per 100,000 people in the United States and is increasing in incidence within a number of cultures worldwide. Likely due to its incompletely understood pathophysiology and etiology, standard treatments for IBD are only efficacious in subsets of patients and often do not induce lasting remission. As a result, novel therapies are needed. The success of anti-tumor necrosis factor-α treatment in a subset of IBD patients demonstrated that therapy targeting a single cytokine could be efficacious in IBD, and clinical trials investigating the blockade of a variety of cytokines have commenced. IL-27 is a relatively recently discovered type I cytokine with established roles in infectious disease, autoimmunity, and cancer in a variety of organs. IL-27 was identified as a candidate gene for IBD, and a number of studies in mouse models of IBD have demonstrated that IL-27 therapy is protective. However, in contrast to these investigations, genetic deletion of the IL-27 receptor has been shown to be protective in some mouse models of IBD. The purpose of this review is to highlight recent literature investigating the role of IL-27 in IBD, and to discuss possible explanations for the sometimes conflicting results of these studies. Evidence supporting IL-27 therapy as a treatment for IBD will also be discussed.

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

“…IL-23 and IL-27 are cytokines thought to be activated in CD, with IL-23 involved in T H 17 differentiation (Sartor, 2006). CD patients have been reported to have increased serum IL-27, but this cytokine may have anti-inflammatory functions due to its ability to trigger IL-10 production (Andrews et al, 2016). IL-23 and IL-27 were increased in the serum of the DSS+FMD FT group (p < 0.05; Figures S5K and S5L), whereas IL-27 was reduced in the colonic supernatant, which was evident in the DSS+FMD FT group (p < 0.05; Figure 5I).…”

IL-27 targets Foxp3+ Tregs to mediate antiinflammatory functions during experimental allergic airway inflammation

“…Despite the fact that there are multiple types of IL-27R + cells capable of responding to the cytokine, our results suggest that Treg response to IL-27 is a requisite for IL-27-induced immune regulation. Since IL-27 is considered a novel therapeutic tool for inflammatory disorders (60,61), improving (or restoring) IL-27 responsiveness of Tregs may be an important goal to achieve in future investigations.…”

Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease

“…Multiple studies have implicated IL-27 gene polymorphism and mutation are associated with the risk of IBD [54]. IL-27 gene expression level is increased in the local colon tissue of patients with active UC or active CD [55].…”

“…IL-27 gene expression level is increased in the local colon tissue of patients with active UC or active CD [55]. The proinflammatory and anti-inflammatory effects of IL-27 have been observed in IBD [54]. Oral delivery of recombinant IL-27 food-grade bacterium Lactococcus lactis ameliorates the murine colitis in a T cell-dependent colitis model, including improving survival, decreasing clinical score and pathologic score, downregulating inflammatory cytokines, and increasing IL-10 [56].…”

“…On the other hand, some studies indicated the proinflammatory roles of IL-27 in IBD based on blocking IL-27 receptor signaling pathway [54]. IL-27R α −/− mice developed less severe intestinal inflammation after DSS treatment when compared to wild-type mice, characterized by reducing inflammatory cytokines (IL-6, TNF, and IFN- γ ).…”