IL-22 associates with Venous Thromboembolism in Inflammatory Bowel Disease: A Hypothesis-Generating Study

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at signifincantly increased risk for venous thromboembolism (VTE). We hypothesized that I) the increased risk is associated with elevated levels of typical pro-inflammatory cytokines and II) that elevated concentrations of specific cytokines could possibly predict a thromboembolic event. METHODS: We examined 226 well characterized patients of the Swiss IBD cohort study (SIBDCS); we analyzed serum samples from 78 IBD patients with documented VTE (n=78) and compared them 2:1 with age and sex matched controls without VTE of the same cohort (n=148) . An array of 12 typical proinflammatory cytokines (IL2, IL17a, IL12p70, IL8, IL1b, IL4, IL5, IFN-γ, IL6, IL22, TNF-α, IL-10) was quantified. Detailed disease characteristics - such as activity (mild, moderat, quiescent) as well as age at visit, sex and the time interval between thrombosis and blood collection were statistically analyzed. RESULTS: IL2, IL17a, IL12p70, IL8, IL1b, IL4, IL5, IFN-γ, IL6, TNF-α, IL-10 showed no statistical difference between the thrombosis and control group. In contrast IL-22 levels (0.709 vs. 0.542 pg/ml, P<0.05) were significantly higher in the VTE group. CONCLUSIONS: IL-22, may associate with an increased risk of VTE in IBD in this hypothesis- generating study, whereas the other inflammatory parameters measured were not associated. This marker appears to be independent of disease activity, as the other cytokines, which are considered markers of disease activity, did not show a significant difference in comparison. Further targeted and serial measurements will have to confirm our findings.