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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

HIV-1 pathogenesis differs in rectosigmoid and tonsillar tissues infected ex vivo with CCR5- and CXCR4-tropic HIV-1.

Gut-associated lymphoid tissue (GALT) has been identified as the primary target of HIV-1 infection. To investigate why GALT is especially vulnerable to HIV-1, and to determine whether the selective transmission of CCR5-using viral variants (R5) in vivo is the result of a greater susceptibility of GALT to this viral variant, we performed comparative studies of CXCR4-using (X4) and R5 HIV-1 infections of human lymphoid (tonsillar) and rectosigmoid tissues ex vivo under controlled laboratory conditions. We found that the relative level of R5 replication in rectosigmoid tissue is much greater than in tonsillar tissue. This difference is associated with the expression of the CCR5 co-receptor on approximately 70% of CD4 T cells in rectosigmoid tissue, whereas in tonsillar tissue it is expressed on fewer than 15% of CD4 T cells. Furthermore, tonsillar tissue responds to X4 HIV-1 infection by upregulating the secretion of CC-chemokines, providing a potential CCR5 blockade and further resistance to R5 infection, whereas gut tissue failed to increase such innate immune responses. Our results show that rectosigmoid tissue is more prone than tonsillar lymphoid tissue to R5 HIV-1 infection, primarily because of the high prevalence and availability of R5 cell targets and reduced chemokine blockade. The majority of CD4 T cells express CXCR4, however, and X4 HIV-1 readily replicates in both tissues, suggesting that although the differential expression of co-receptors contributes to the GALT vulnerability to R5 HIV-1, it alone cannot account for the selective R5 infection of the rectal mucosa in vivo.

Granulomatous inflammation in sigmoid diverticulitis: two diseases or one?

AIMS: Histological appearances indistinguishable from Crohn's disease have been described in patients undergoing sigmoid colectomy for complicated diverticular disease. To investigate whether this finding represents coincidental dual pathology or merely a granulomatous colitis confined to the diverticular segment, we undertook clinical follow-up of affected patients. METHODS AND RESULTS: Eight patients (median age 64 years, four males) whose sigmoid colectomy specimens showed acute diverticulitis and granulomatous inflammation were identified. All had a pre-operative diagnosis of diverticular disease and no previous evidence of Crohn's disease. Non-caseating epithelioid granulomas, unrelated to foreign material and usually unrelated to inflamed diverticular were present in the bowel wall of seven cases and in the regional lymph nodes of five. Three had granulomatous vasculitis and two had granulomas in 'background' mucosa. Mural lymphoid aggregates were identified in all cases. However, fissuring ulcers distinct from inflamed diverticula were not identified. On median follow-up of 51 months (range 18-112 months) none of the patients developed evidence of chronic inflammatory bowel disease. Three had died from unrelated causes. CONCLUSIONS: Granulomatous inflammation appears to be part of a spectrum of sigmoid diverticulitis. In this setting, caution should be exercised to avoid an inappropriate diagnosis of Crohn's disease.