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

Abstract

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.

Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels

“…However, this is—to our knowledge—the first time that this association is formally demonstrated. The fundamental role of neutrophil infiltration in the mucosa in the pathophysiology of UC has long been acknowledged, and its association with endoscopic severity and systemic inflammatory indexes such as C reactive protein levels has been previously demonstrated 35. Targeting neutrophils is, indeed, a possible therapeutic approach that ought to be further explored.…”

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

“…Neutrophil migration into the colon mucosa is a hallmark of inflammatory bowel diseases, but still differences exist between UC and CD [29]. In UC, neutrophil accumulation in stool of patients positively correlates with active disease [30] and neutrophil infiltration is associated with the severity of the disease [11].…”

Sphingolipids in neutrophil function and inflammatory responses: Mechanisms and implications for intestinal immunity and inflammation in ulcerative colitis

“…Currently, the global burden of UC is on the rise, with an increased incidence in several regions of the world, primarily in developing countries. In the United States, the incidence is approximate 20 per 100,000 person-years and the prevalence at approximately 250 cases per 100,000 persons (Muthas et al, 2016). Disease progression and chronic inflammation can result in ulceration, mucin depletion and loss of crypt architecture.…”

“…The transmigration of activated neutrophils through epithelial paracellular and gap junctions, and their accumulation in the crypt lumen results in the formation of crypt abscesses, the characteristic histological lesions of UC. Breaching of the epithelial barrier increases permeability, facilitating the translocation of luminal bacteria into the lamina propria (Fournier and Parkos, 2012; Muthas et al, 2016). The persistence of activated neutrophils in the intestinal mucosa underscores the dysfunction in regulatory mechanisms of intestinal homeostasis.…”

“…The degree of neutrophil density in the tissue may be an important determinant of their role in disease (Nathan, 2006). Calprotectin, a neutrophil derived protein complex, has been identified as a biomarker in UC and the levels correlate with the degree of neutrophil infiltrate in the gut (Muthas et al, 2016; Pruenster et al, 2016). The relevance of calprotectin as a metric of disease index in UC indicates that the complex regulation of neutrophil infiltration into the tissue may represent an important research area to block UC pathogenesis.…”