On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

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.

Serum inflammatory markers in the diagnosis and assessment of Crohn’s disease activity

“…IL-6 is also a candidate marker for CD course and treatment monitoring. It was demonstrated to be associated with disease activity [ 22 – 25 ], to predict endoscopic IBD activity in combination with serum amyloid A (SAA), IL-8, and eotaxin-1 [ 26 ], and to predict the response to biologic treatment in CD patients [ 27 , 28 ]. However, there are also reports that do not confirm the diagnostic utility of IL-6 in CD [ 29 ].…”

Oral Manifestations of Inflammatory Bowel Disease and the Role of Non-Invasive Surrogate Markers of Disease Activity

“…In fact, although many factors (such as infectious agents, diet, drugs, smoking) have been investigated, a precise causal agent, or a cluster of agents, has not been identified. In the last few years, a role of GI microbiota in the pathogenesis of IBD has been proposed [11]. The human GI microbiota consists of a wide variety of bacteria, viruses, fungi and other single-celled organisms.…”

Pomegranate Mesocarp against Colitis-Induced Visceral Pain in Rats: Effects of a Decoction and Its Fractions

“…As chronic conditions affecting the gut, IBDs and IBS present some clinical overlap like abdominal pain, alterations of intestinal transit, and they both tend to be diagnosed in young people [23,24]. In IBDs, patients upregulated expression of cytokines (such as TNF-α, IL-6, IL-12, IL-17) and substance P [25,26], and alterations in gut microbiota [27] were observed, as well as significantly increased numbers of mast cells in the mucosa of the ileum and colon [28], even in IBS patients [29]. Mast cells play a very important role in the regulation of intestinal permeability and, being below the intestinal mucosa barrier, can be activated by microbial antigens [30,31].…”