Immune system alterations in patients with inflammatory bowel disease during remission

Jurgita Šventoraitytė,Rimantas Žalinkevičius,Vytas Tamošiūnas,Antanas Praškevičius,Limas Kupčinskas,Aurelija Žvirblienė,Gediminas Kiudelis,Aida Žvirblienė

doi:10.3390/medicina44010005

Jurgita Šventoraitytė, Rimantas Žalinkevičius + Show 6 more

Open Access

https://doi.org/10.3390/medicina44010005

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Abstract

Perturbed immune homeostasis elicited by misbalanced production of proinflammatory and anti-inflammatory cytokines is characteristic of inflammatory bowel disease. The aim of this study was to evaluate cytokine profile in patients with different forms of inflammatory bowel disease - ulcerative colitis and Crohn's disease - during clinical remission phase. Production of proinflammatory Th1 cytokines (tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma)) and anti-inflammatory Th2 cytokines (interleukin-10 (IL-10) and interleukin-13 (IL-13)) was analyzed in peripheral blood mononuclear cells of patients with inflammatory bowel disease (9 with ulcerative colitis and 9 with Crohn's disease) and control subjects (n=11) by enzyme-linked immunosorbent assay (two-site ELISA). The results of the study revealed that the level of TNF-alpha after stimulation with phytohemagglutinin in patients with Crohn's disease was significantly higher in comparison to both patients with ulcerative colitis and controls (P<0.001 and P<0.01, respectively). The secretion of IFN-gamma both in patients with Crohn's disease and ulcerative colitis was lower than that in controls (P=0.05 and P<0.01, respectively), but it normalized after stimulation with phytohemagglutinin. The levels of IL-10 and IL-13 were significantly (P<0.01) higher in patients with Crohn's disease than in patients with ulcerative colitis and control group before and after stimulation with phytohemagglutinin. The results of our study provide evidence that in patients with inflammatory bowel disease, the imbalance between production of proinflammatory Th1 and anti-inflammatory Th2 cytokines persists even during remission of the disease, and disturbances of immune homeostasis are significantly more expressed in patients with Crohn's disease than in patients with ulcerative colitis.

Highlights

Ulcerative colitis (UC, OMIM 191390) and Crohn’s disease (CD, OMIM 266600), collectively referred to the inflammatory bowel disease (IBD), represent a group of multifactorial autoimmune disorders of the gastrointestinal tract sharing many clinical and pathological characteristics, differing in histological features and cytokine profiles [1,2,3]
The results of our study provide evidence that in patients with inflammatory bowel disease, the imbalance between production of proinflammatory Th1 and anti-inflammatory Th2 cytokines persists even during remission of the disease, and disturbances of immune homeostasis are significantly more expressed in patients with Crohn’s disease than in patients with ulcerative colitis
The etiology of IBD is still unknown, the animal model and human case-control studies have revealed that in the intestinal tissue and peripheral blood during active CD phase, the levels of tumor necrosis factor-alpha (TNF-a), interferongamma (IFN-g), interleukin (IL)-12 and IL-1 are increased, whereas in ulcerative colitis (UC), the secretion of IL-5, IL-4, IL-10, and IL-13 is upregulated, elucidating that immune mechanisms playing a major role in the initiation and perpetuation of both diseases are distinct

Summary

Introduction

Ulcerative colitis (UC, OMIM 191390) and Crohn’s disease (CD, OMIM 266600), collectively referred to the inflammatory bowel disease (IBD), represent a group of multifactorial autoimmune disorders of the gastrointestinal tract sharing many clinical and pathological characteristics, differing in histological features and cytokine profiles [1,2,3]. The etiology of IBD is still unknown, the animal model and human case-control studies have revealed that in the intestinal tissue and peripheral blood during active CD phase, the levels of tumor necrosis factor-alpha (TNF-a), interferongamma (IFN-g), interleukin (IL)-12 and IL-1 are increased, whereas in UC, the secretion of IL-5, IL-4, IL-10, and IL-13 is upregulated, elucidating that immune mechanisms playing a major role in the initiation and perpetuation of both diseases are distinct. Results achieving statistical significance for a distinction between cases and controls are shown in bold

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