Markers of Hypoxia Correlate with Histologic and Endoscopic Severity of Colitis in Inflammatory Bowel Disease

Abstract

Background:

Inflammation results in significant shifts in tissue metabolism. Recent studies indicate that inflammation and hypoxia occur concomitantly. We examined whether circulating and tissue markers of hypoxia could serve as surrogate indicators of disease severity in adult and pediatric patients with inflammatory bowel disease (IBD).

Methods:

Serum and colonic biopsies were obtained from pediatric subjects with active IBD colitis and adult subjects with active and inactive ulcerative colitis, along with healthy non-colitis controls of all ages. Disease activity was evaluated by endoscopy and histopathology. Levels of serum hypoxia markers (macrophage inflammatory protein-3α [MIP-3α], vascular endothelial growth factor [VEGF], and erythropoietin [EPO]) were measured.

Results:

Children with active IBD colitis had higher levels of serum MIP-3α and VEGF compared to non-colitis controls (p<0.01 and p<0.05, respectively). In adult subjects with endoscopically active ulcerative colitis, serum MIP-3α and EPO were significantly elevated compared to non-colitis controls (both p<0.01). In parallel, analysis of colon tissue MIP-3α mRNA and protein in pediatric subjects revealed increased expression in those with IBD colitis compared to controls (p<0.05 and p<0.01 for mRNA and protein, respectively). Serum MIP-3α and VEGF significantly increased with histology grade.

Conclusion:

Peripheral blood hypoxia markers may be useful indicators of disease activity for pediatric and adult IBD patients.

Keywords:

• Crohn’s disease
• ulcerative colitis
• mucosal inflammation
• tissue histology

Acknowledgment

We would like to acknowledge Kelley Capocelli, MD for providing histology photomicrographs.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

Dr Steven B. Colson reports T32 Training grants from NIH, during the conduct of the study. Dr Robert Isfort was a speaker for Takeda Pharmaceuticals, outside the submitted work. Dr Simon Keely reports grants from GossamBio, NHMRC, Cancer institute NSW, and Anatara Life Sciences, personal fees from Aerpio Therapeutics, Gossamer Bio, Anatara Life Sciences, outside the submitted work. The authors report no other conflicts of interest in this work.