Significance of serum Il-9 levels in inflammatory bowel disease

Abstract

IL-9, which may be an inflammatory or regulatory cytokine, can be experimentally produced in a Th17 or modified Th2 context in the presence of T cell receptor (TCR) stimulation. The primary aim of this study was to measure serum IL-9 levels in patients with inflammatory bowel disease (IBD), and evaluate their relationships with the patients' clinical characteristics. The secondary aim was to determine the levels of interferon-γ (IFN (interferon)-γ), Th2 cytokines (IL-4, IL-5 and IL-13), and IL-6 in order to clarify the context of detectable peripheral cytokines in which IL-9 is produced.Venous blood samples of 43 IBD patients (20 with Crohn's disease [CD] and 23 with ulcerative colitis [UC]) were analysed by means of quantitative enzyme-linked immunosorbent assays using purified anti-human IL-4, IL-5, IL-13, IFN-γ, IL-9 and IL-6 antibodies, and the laboratory findings were statistically correlated with their clinical expression.None of the patients showed the peripheral presence of IL-4, IL-5 and IL-13. Forty (93%) were positive for IFN-γ, thus confirming the presence of Th1 in both UC and CD, and IFN-γ levels correlated with disease activity (P = 0.045). Eighteen patients (41%) were positive for IL-9, which was associated with a severe prognosis (P <0.001), and 72.2% of the IL-9-positive patients were also IL-6 positive. There was a significant correlation between disease severity and IL-9 in the CD patients (P <0.001), but not in the UC patients (P = 0.1).Our findings confirm the presence of common Th1 cytokines in UC and CD. However the IL-9 positivity indicates the presence of an alternative population of T cells that respond to antigen stimulation and condition the prognosis of IBD. The fact that the same serum IL-9 levels were differentially associated with clinical measures of CD and UC activity suggest that the same cytokine can be produced in different contexts.

Systemic interleukin-9 in inflammatory bowel disease: Association with mucosal healing in ulcerative colitis

“…Unlike the cytokine tissue expression, preferential in UC[9,10], circulating IL9 did not differ between CD and UC in either Defendenti et al[13] or our cohorts. However, we observed a divergent association pattern with inflammatory and angiogenic indices that might translate into functional differences in IL9 between both conditions.…”

“…Defendenti et al[13] were the first to report on an elevation of circulating IL9 in IBD and link this finding to severe prognosis. Using a more sensitive, fluorescence-based assay for cytokine determination, our research corroborates their findings on a larger set of patients, but focuses on IL9 as a possible MH marker.…”

“…Only recently, the elevation of serum IL9 in IBD has been reported and linked with severe prognosis[13]. Supplementing this pioneering research, we aimed to assess circulating cytokines with reference to a large cohort of patients and present these data in the context of other cytokines: proinflammatory (IL1β, IL6, TNFα) and angiogenic (VEGF-A), and of Th1 (IFNγ and TNFα) and Th2 (IL13) subset signatures as well as symptoms accompanying IBD, namely, anemia and cachexia.…”

Pathogenic T cell subsets in allergic and chronic inflammatory bowel disorders

“…Consistently, IL‐9 expression in T cells and IL‐9R expression in IECs from UC patients was found to be significantly elevated . Recently, IL‐9 was also detected in the serum of IBD patients . IL‐9 is therefore considered a potential target for future therapy in UC patients .…”

“…135 Recently, IL-9 was also detected in the serum of IBD patients. 136 IL-9 is therefore considered a potential target for future therapy in UC patients. 137 Interestingly, Th9 cells seem to express especially high levels of αEβ7 integrin favoring their epithelial retention in the gut and suggesting that these cells might be a main target of the anti-αEβ7 antibody etrolizumab currently investigated in phase III trials.…”