A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis

Abstract

Inflammatory bowel disease (IBD) is a lifelong inflammatory immune mediated disorder, encompassing Crohn’s disease (CD) and ulcerative colitis (UC); however, the cause and specific pathogenesis of IBD is yet incompletely understood. Multiple cytokines produced by different immune cell types results in complex functional networks that constitute a highly regulated messaging network of signaling pathways. Applying biological mechanisms underlying IBD at the single omic level, technologies and genetic engineering enable the quantification of the pattern of released cytokines and new insights into the cytokine landscape of IBD. We focus on the existing literature dealing with the biology of pro- or anti-inflammatory cytokines and interactions that facilitate cell-based modulation of the immune system for IBD inflammation. We summarize the main roles of substantial cytokines in IBD related to homeostatic tissue functions and the remodeling of cytokine networks in IBD, which may be specifically valuable for successful cytokine-targeted therapies via marketed products. Cytokines and their receptors are validated targets for multiple therapeutic areas, we review the current strategies for therapeutic intervention and developing cytokine-targeted therapies. New biologics have shown efficacy in the last few decades for the management of IBD; unfortunately, many patients are nonresponsive or develop therapy resistance over time, creating a need for novel therapeutics. Thus, the treatment options for IBD beyond the immune-modifying anti-TNF agents or combination therapies are expanding rapidly. Further studies are needed to fully understand the immune response, networks of cytokines, and the direct pathogenetic relevance regarding individually tailored, safe and efficient targeted-biotherapeutics.

Cytokine Signatures in Inflamed Mucosa of IBD Patients: State-of-the-Art

“…Sensitivity and specificity issues are common, as some techniques may lack the sensitivity to detect low-abundance cytokines or the specificity to distinguish between closely related cytokine isoforms. Additionally, standardization challenges across different platforms and laboratories can lead to variability in results, making it difficult to compare findings between studies or establish robust diagnostic criteria [87].…”

Genetic Overlap Between Inflammatory Bowel Disease and Neurological Disorders: Insights from GWAS and Gene Expression Analysis

“…The enrichment of BP terms like Cytokine Production and Regulation of Cytokine Production suggest a possible central role of cytokine networks in CD pathophysiology. Such networks facilitate cell communication during immune responses (Alhendi A, Naser S, 2023;Vebr M et al, 2023).…”

“…The NF-Kappa B Signaling Pathway and Cytokine-Cytokine Receptor Interaction pathways are also shared between UC and CD, emphasizing their central role in regulating immune responses and inflammation in both conditions (Atreya I, Atreya R, Neurath M, 2008;Vebr M et al, 2023). These pathways are integral to the broader IBD pathology, underscoring the shared mechanisms underlying these diseases.…”

Role of IL-33/ST2 Pathway in Inflammatory Bowel Disease: An Overview and Future Perspectives

“…In CD, histological examination reveals a thickened submucosa, transmural inflammation, fissuring ulceration, and granulomas [12]. On the other hand, UC is characterized by inflammation limited to the mucosa and submucosa, typically presenting with superficial mucosa erosions, cryptitis, and crypt abscesses [13][14][15]. Although some therapeutic drugs may be effective for both UC and CD, patients with these conditions often undergo different clinical treatment approaches and vary as to optimal timing for surgical intervention as well as respective complications.…”