The local intestinal interstitial cytokine profile provides an insight into inflamed bionaive patients with Ulcerative Colitis​​​​​

Background: Proinflammatory cytokines identified in the mucosal microenvironment at the site of inflammation are involved in the pathophysiology of inflammatory bowel diseases such as ulcerative colitis (UC). We hypothesize that the local cytokine production is significantly altered in inflamed regions of the intestine and cannot be predicted by plasma measurements.

Aims: Our goal is to identify personalized cytokine signatures in UC patients' interstitial space depending on their disease progression. This advances our understanding of UC and can support the development of more personalized treatment strategies as cytokine signaling is a target of current therapies.

Methods: We isolated interstitial fluid (IF) from the intestinal mucosa using the tissue elution method in bionaive UC patients (mild activity (UCEIS 1-4) n=6; inflamed (UCEIS 5-8) n=6) and healthy controls (n=25) as part of the InFlame study (DRKS00031203). We took biopsies from rectum, descending colon, ascending colon and ileum in 400mg NaCl for 2h elution in 4°C. Obtained IF was used for multiplex immunoassays of 18 proinflammatory cytokines in the same way as plasma cytokines.

Results: VEGF, IL-16 and IL-12p40 are present in healthy controls and inflamed patients in the IF. Depending on the disease's severity, more cytokines can be detected. Cytokine concentrations increase in the more aboral localizations of the colon with the rectum showing a unique cytokine pattern. Cytokines that can be detected in plasma show much lower concentrations compared to IF. Inflamed patients can be distinguished from mild activity in local interstitial profiles. In plasma and rectum different cytokines appear to drive inflammation – those can be identified by linear discriminant analysis. Moreover, rectal interstitial cytokine patterns correlate well with endoscopic and clinical UC scores.

Conclusion: Isolation of IF is a valuable approach to assessing inflammation in UC patients, improving our understanding of mild residual activity and more severe conditions. We can identify cytokines that drive inflammation in UC and characterize the inflammatory intestinal cytokine profile associated with a healthy gut. Future targeted therapies should also consider the unique cytokine profiles of individuals being expressed in the rectum. Comparing bionaive cytokine profiles with profiles from patients treated with biologicals, will allow us to demonstrate how the network changes in response to immunosuppression.

 

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Publication History

Article published online:
04 September 2025