Can We Target Endogenous Anti-inflammatory Responses as a Therapeutic Strategy for Inflammatory Bowel Disease?

Abstract

Inflammatory bowel disease (IBD) describes chronic relapsing remitting inflammation of the gastrointestinal tract including ulcerative colitis and Crohn's disease. The prevalence of IBD is rising across the globe. Despite a growing therapeutic arsenal, current medical treatments are not universally effective, do not induce lasting remission in all, or are accompanied by short- and long-term adverse effects. Therefore, there is a clinical need for novel therapeutic strategies for IBD. Current treatments for IBD mainly manipulate the immune system for therapeutic gain by inhibiting pro-inflammatory activity. There is a robust endogenous immunoregulatory capacity within the repertoire of both innate and adaptive immune responses. An alternative treatment strategy for IBD is to hijack and bolster this endogenous capability for therapeutic gain. This review explores this hypothesis and presents current evidence for this therapeutic direction in immune cell function, cytokine biology, and alternative mechanisms of immunoregulation such as microRNA, oligonucleotides, and the endocannabinoid system.

Serum Amyloid A Promotes Inflammation-Associated Damage and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer

“…Accordingly, the identification of such molecules that can be targeted remains a strong focus in the search for effective therapies. [3][4][5] Serum amyloid A (SAA) is a family of evolutionary conserved proteins implicated in inflammation. 6,7 SAA1 and SAA2 are prominent acute-phase proteins and systemic levels are up-regulated significantly upon inflammatory or infectious stimuli, peaking 24-48 hours after stimulus before returning to low baseline levels.…”

Mapping genetic determinants of 184 circulating proteins in 26,494 individuals to connect proteins and diseases

“…There are conflicting data on IL27's role in IBD. In most 47,48 , although not all 49 , murine models of gut inflammation, IL27 is protective: IL27R genetic knockout worsens colitis while exogenous administration of IL27 ameliorates disease. In patients with IBD, IL27 gene expression is elevated compared to controls 50 .…”

Thymosin α1 protects from CTLA-4 intestinal immunopathology

“…However, it remains unexplored whether any measure could be taken to prevent, rather than cure, ICI-induced colitis (Som et al, 2019). One possibility relies on coopting endogenous mechanisms of tolerance and protection as a strategy to restore or maintain mucosal homeostasis (Porter et al, 2018), which may include immune cell types, such as regulatory T cells or tolerogenic DCs, and cytokines (Porter et al, 2018).…”