Complement activation capacity in plasma before and during high-dose prednisolone treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by intestinal inflammation mainly caused by a disturbance in the balance between cytokines and increased complement (C) activation. Our aim was to evaluate possible associations between C activation capacity and prednisolone treatment. METHODS: Plasma from patients with exacerbations of UC (n = 18) or CD (n = 18) were collected before and during high dose prednisolone treatment (1 mg/kg body weight) and tapering. Friedman's two way analysis of variance, Mann-Whitney U test and Wilcoxon signed-rank sum test were used RESULTS: Before treatment, plasma from CD patients showed significant elevations in all C-mediated analyses compared to the values obtained from 38 healthy controls (p < 0.02), and in mannan binding lectin (MBL)-concentration and MBL-C4-activation capacity (AC) values compared to UC patients (p < 0.02). Before treatment, plasma from UC patients showed significant elevations only in the classical pathway-mediated C3-AC compared to values obtained from healthy controls (p < 0.01). After treatment was initiated, significant reductions, which persisted during follow-up, were observed in the classical pathway-mediated C3-AC and MBL-C4-AC in plasma from CD patients (p < 0.05). CONCLUSION: Our findings indicate that C activation capacity is up-regulated significantly in plasma from CD patients. The decreases observed after prednisolone treatment reflect a general down-regulation in immune activation

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so

Effects of perioperative supplementation with omega-3 fatty acids on leukotriene B4 and leukotriene B5 production by stimulated neutrophils in patients with colorectal cancer: a randomized, placebo-controlled intervention trial

Omega-3 fatty acids (n-3 FA) may have beneficial clinical and immune-modulating effects in surgical patients. In a randomized, double-blind, prospective, placebo-controlled trial, 148 patients referred for elective colorectal cancer surgery received an n-3 FA-enriched oral nutritional supplement (ONS) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for seven days before surgery. On the day of operation, there was a significant increase in the production of leukotriene B5 (LTB5) (p &lt; 0.01) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p &lt; 0.01), a significant decrease in the production of leukotriene B4 (LTB4) (p &lt; 0.01) and a trend for a decrease in the production of 5-hydroxyeicosatetraenoic acid (5-HETE) (p &lt; 0.1) from stimulated neutrophils in the active group compared with controls. There was no association between LTB4 values and postoperative complications. In conclusion, oral n-3 FA exerts anti-inflammatory effects in surgical patients, without reducing the risk of postoperative complications