Neutrophils in ulcerative colitis: a review of selected biomarkers and their potential therapeutic implications

Abstract

Objectives: This review article describes the role of neutrophils in mucosal injury and the resulting crypt abscesses characteristic of ulcerative colitis. We also review selected biomarkers for monitoring neutrophil presence and activity in the mucosa as well as their potential as therapeutic targets.

Material: We have collated and selectively reviewed data on the most prominent well-established and emerging neutrophil-related biomarkers and potential therapeutic targets (calprotectin, lactoferrin, CXCR1, CXCR2, MMP-9, NGAL, elafin, HNE, pANCAs, MPO, CD16, CD177, CD64, HNPs, SLPI and PTX3) in ulcerative colitis.

Results: Systemic and intestinal neutrophil activity increases substantially in active ulcerative colitis, driving tissue damage and extra-intestinal manifestations. Calprotectin is a robust neutrophil and disease biomarker, and a few neutrophil-related targets are being clinically explored as therapeutic targets.

Conclusion: We propose that targeting neutrophils and their inflammatory mediators per se is an opportunity that should be explored to identify new effective medical therapies. The overall clinical goal for neutrophil-targeted therapy will be to modulate, but not completely silence, neutrophil activity, thereby abolishing the destructive inflammation with associated acute and chronic tissue damage without compromising host-defense.

Keywords:

• Ulcerative colitis
• neutrophils
• biomarkers
• inflammation
• clinical development
• mucosa
• Therapy

Disclosure statement

SD has served as a speaker, a consultant and an advisory board member for Abbott Laboratories, Abbvie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Hospira, Genentech, Grunenthal, Johnson and Johnson, Merck, Millennium Takeda, Mundipharma, Novo Nordisk, Nycomed, Pfizer Inc, Pharmacosmos Tigenix, UCB Pharma, Vifor. MBH and IGC are former employees of AstraZeneca.

Funding

TTM received research funding from GSK, Janssen, VH2, Kymab, Topivert and Grunenthal.