Chemokine and cytokine levels in inflammatory bowel disease patients

Abstract

Crohn's disease (CD) and ulcerative colitis (UC), two forms of inflammatory bowel disease (IBD), are chronic, relapsing, and tissue destructive lesions that are accompanied by the uncontrolled activation of effector immune cells in the mucosa. Recent estimates indicate that there are 1.3 million annual cases of IBD in the United States, 50% of which consists of CD and 50% of UC. Chemokines and cytokines play a pivotal role in the regulation of mucosal inflammation by promoting leukocyte migration to sites of inflammation ultimately leading to tissue damage and destruction. In recent years, experimental studies in rodents have led to a better understanding of the role played by these inflammatory mediators in the development and progression of colitis. However, the clinical literature on IBD remains limited. Therefore, the aim of this study was to evaluate systemic concentrations of key chemokines and cytokines in forty-two IBD patients with a range of disease activity compared to levels found in ten healthy donors. We found a significant increase in an array of chemokines including macrophage migration factor (MIF), CCL25, CCL23, CXCL5, CXCL13, CXCL10, CXCL11, MCP1, and CCL21 in IBD patients as compared to normal healthy donors (P<0.05). Further, we also report increases in the inflammatory cytokines IL-16, IFN-γ, IL-1β and TNF-α in IBD patients when compared to healthy donors (P<0.05). These data clearly indicate an increase in circulating levels of specific chemokines and cytokines that are known to modulate systemic level through immune cells results in affecting local intestinal inflammation and tissue damage in IBD patients. Blockade of these inflammatory mediators should be explored as a mechanism to alleviate or even reverse symptoms of IBD.

Keywords: Chemokine; Crohn’s disease (CD); Cytokine; Inflammation; Inflammatory bowel disease (IBD); Ulcerative colitis (UC).

Published by Elsevier Ltd.

Figures

Fig. 1

Serum level of MIF, CCL21, CCL23, CCL25, I-309, and MCP-1 during IBD. Sera from IBD patients (n = 42, ■) and normal healthy donors (n = 10 □) were isolated and evaluated for the presence of CC chemokines (MIF, CCL21, CCL23, CCL25, I-309 and MCP-1) by multiplex ELISA that was capable of detecting >10 pg/ml of each chemokines. The data presented are the mean MIF, CCL21, CCL23, CCL25, I-309, and MCP-1 concentrations ± SEM in IBD patients and healthy donors. Asterisk(s) indicate statistically significant differences, i.e., p < 0.05 (*), between the two groups.

Fig. 2

Systemic levels of CXCL5, CXCL6, CXCL10, CXCL11, and CXCL13 during IBD. Sera from IBD patients (n = 42, ■) and normal healthy donors (n = 10 □) were isolated and evaluated for the presence of CXC chemokines (CXCL5, CXCL6, CXCL10, CXCL11, and CXCL13) by multiplex ELISA that was capable of detecting >10 pg/ml of each chemokines. The data presented are the mean CXCL5, CXCL6, CXCL10, CXCL11, and CXCL13 concentrations ± SEM in IBD patients and healthy donors. Asterisk(s) indicate statistically significant differences, i.e., p < 0.05 (*), between the two groups.

Fig. 3

Changes in systemic TNF-α, IL-1β, IFN-γ and IL-16 cytokines level during IBD. Sera from IBD patients (n = 42, ■) and normal healthy donors (n = 10 □) were isolated and evaluated for the presence of cytokines (TNF-α, IL-1β, IFN-γ and IL-16) by multiplex ELISA that was capable of detecting >10 pg/ml of each chemokines. The data presented are the mean TNF-α, IL-1β, IFN-γ and IL-16 concentrations ± SEM in IBD patients and healthy donors. Asterisk(s) indicate statistically significant differences, i.e., p < 0.05 (*), between the two groups.