Abstract
In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.
Highlights
Inflammatory bowel diseases (IBD) are chronic intestinal disorders consisting of two disease entities, Crohn’s disease (CD) and ulcerative colitis (UC), both characterized by an immune-mediated pathogenesis and a clinical relapsing course [1,2]
It has been shown that serum zonulin levels are increased in patients with inflammatory bowel disease (IBD) compared to healthy controls [8] (while no studies are present in the literature comparing levels in patients with IBD and levels in patients with gastrointestinal symptoms without clear inflammation, like patients affected by irritable bowel symptoms (IBS)) and are associated with higher levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα) and interleukin (IL)-6 [9], which play a key role in promoting mucosal inflammation [10]
Increased levels of circulating soluble(s)-CD163, a macrophage activation marker, was associated with active CD and UC showing higher values in IBD patients compared to healthy subjects; in addition, soluble CD163 values showed a decrease over the course of treatment, reaching levels similar to those observed in the healthy population [11]
Summary
Inflammatory bowel diseases (IBD) are chronic intestinal disorders consisting of two disease entities, Crohn’s disease (CD) and ulcerative colitis (UC), both characterized by an immune-mediated pathogenesis and a clinical relapsing course [1,2]. The exact etiology of IBD is unknown, but it is supposed that impaired intestinal permeability, together with genetic, microbial, and environmental factors, contributes to the onset of the disease [3,4,5]. It has been shown that serum zonulin levels are increased in patients with IBD compared to healthy controls [8] (while no studies are present in the literature comparing levels in patients with IBD and levels in patients with gastrointestinal symptoms without clear inflammation, like patients affected by irritable bowel symptoms (IBS)) and are associated with higher levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα) and interleukin (IL)-6 [9], which play a key role in promoting mucosal inflammation [10]. Increased levels of circulating soluble(s)-CD163, a macrophage activation marker, was associated with active CD and UC showing higher values in IBD patients compared to healthy subjects; in addition, soluble CD163 (sCD163) values showed a decrease over the course of treatment, reaching levels similar to those observed in the healthy population [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
