Association of steroid use with complicated sigmoid diverticulitis: potential role of activated CD68+/CD163+ macrophages

Abstract

Immunosupression and, especially, intake of steroids have previously been identified as risk factors for complicated types of sigmoid diverticulitis. However, little is known about the underlying molecular and cellular mechanisms. We aimed to elucidate the potential role of activated macrophages in this respect. A consecutive series of n = 101 patients having undergone surgical resection for sigmoid diverticulitis at our institution was analyzed regarding the inflammatory infiltrate and prevalence of comorbid diseases as well as risk factors, including steroid use. Fifty-seven patients had complicated types of diverticulitis with severe inflammation (group A). Forty-four patients had moderate inflammation, most of whom had been operated for chronically recurrent diverticulitis (group B). Randomly selected 50 patients (n = 20/group A/n = 30 group B) underwent immunolabelling against CD68 and CD163. Using immunofluorescence double labeling experiments we found a strong positive correlation of CD68 expression with CD163 expression (т = 0.934). High CD68 expression (x ≥ 23%) and high CD163 expression (x ≥ 22%) within stromal cells of the lamina propria was significantly associated with steroid use (CD68, p = 0.012 and CD163, p = 0.004, respectively) and complicated sigmoid diverticulitis with severe inflammation (CD68, p = 0.0001 and CD163, p = 0.001, respectively). Inflammation, especially mediated by activated (CD68+/CD163+) macrophages in histopathological specimen might resemble the cellular link between steroid use and complicated types of sigmoid diverticulitis. Macrophages might be a suitable target for future supportive/preventive therapies. However, as long as we are lacking such strategies, we must bear in mind that steroid intake is a risk factor for complicated diverticulitis, especially when indicating surgical resection.