Anti-inflammatory and anticoagulant properties of the protein C system in inflammatory bowel disease.

INTRODUCTION: In patients with inflammatory bowel disease (IBD), disbalance between procoagulant, anticoagulant, and fibrinolytic factors has been shown. The hemostatic system is an indispensable component of the inflammatory process. Deficiencies in the protein C (PC) pathway components not only promote thrombosis, but also exacerbate inflammation. OBJECTIVES: The aim of the study was to assess the components of the PC system and their correlations with disease activity in patients with IBD. PATIENTS AND METHODS: The levels of PC, free protein S (PS), and soluble thrombomodulin (sTM) were measured in 55 consecutive patients with ulcerative colitis (UC), 50 patients with Crohn's disease (CD), and 41 healthy volunteers. Correlations between PC system components and disease activity, hemostatic variables, and inflammatory markers were assessed. RESULTS: sTM levels in patiens with UC were higher compared with controls (24.5 vs. 17.5 ng/ml; P = 0.0042). In patients with IBD, PC activity was higher and PS activity was lower compared with controls (P <0.001). Tumor necrosis factor α (TNF-α) levels were higher in patients with IBD, and interleukin 6 (IL-6) levels were higher only in patients with CD. In patients with UC, a positive correlation was observed between sTM and both PC and PS levels (r = 0.28 and r = 0.34, respectively, P <0.05). Only PC levels correlated with UC activity (r = 0.3, P <0.05). No correlations of TNF-α, IL-6, and C-reactive protein with PC, PS, and sTM levels were observed. CONCLUSIONS: The PC pathway is defective in patients with CD and UC. Hypercoagulability in IBD might be associated not only with the inflammatory process but also with disturbances in the anticoagulant system, since defective PC pathway was observed both in active and nonactive disease.

Proinflammatory cytokines in the saliva of patients with active and non-active Crohn's disease.

INTRODUCTION:  Crohn's disease (CD) involves the entire gastrointestinal tract, including the mouth. Numerous cytokines play a role in the regulation of inflammatory process in CD. OBJECTIVES:  The aim of the study was to examine the prevalence of oral lesions in adult patients with CD and to investigate whether salivary concentrations of interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) are associated with the activity and oral manifestations of CD. PATIENTS AND METHODS:  A prospective study included 95 adult patients: 52 with active CD and 43 with inactive CD. The control group involved 45 subjects without CD. We performed blood tests, careful oral examination, and measurement of IL-1ß, IL-6, and TNF-α in unstimulated whole saliva by enzyme-linked immunosorbent assays. RESULTS:  IL-1ß, IL-6, and TNF-α were significantly elevated in patients with active CD. IL-1ß levels were 289.8 ±52.7 in patients with active CD vs. 196.7 ±42.9 pg/ml in patients with inactive CD (P <0.039), and 196.7 ±42.9 pg/ml (P <0.01) in controls. IL-6 levels were 13.8 ±4.2 vs. 7.2 ±3.1 pg/ml (P <0.041), respectively, and 6.3 ±1.4 pg/ml (P <0.001) in controls. TNF-α levels were 32.5 ±8.7 vs. 10.2 ±6.3 pg/ml (P <0.002), respectively, and 6.8 ±2.8 pg/ml (P <0.001) in controls. We observed CD-specific oral lesions: diffuse asymptomatic buccal swelling in 12 patients (23%) and cobblestoning in 5 patients (11.3%). CD-nonspecific lesions were observed in 17 patients (32.7%) with active CD, in 11 patients (25.6%) with inactive CD, and in 6 controls (13.3%). In active CD, higher salivary IL-6 and TNF-α and serum C-reactive protein levels correlated with specific oral lesions. CONCLUSIONS:  In patients with active CD, salivary IL-1ß, IL-6, and TNF-α levels are higher than in patients with inactive disease and controls. Elevated salivary IL-6 and TNF-α levels correlate with specific oral lesions. These cytokines may be used as markers of active CD, but the finding should be confirmed in a larger group of patients.

Efficacy of pegylated interferon alfa-2a or alfa-2b in combination with ribavirin in the treatment of chronic hepatitis caused by hepatitis C virus genotype 1b.

INTRODUCTION: Treatment of chronic hepatitis C (CHC) with pegylated interferon (Peg-IFN) and ribavirin leads to sustained virological response (SVR) in approximately 50% of the patients. SVR depends on hepatitis C virus (HCV) and host factors, including IL28B genotypes. OBJECTIVES: The aim of the study was to investigate the therapeutic efficacy of the difficult-to-treat HCV genotype 1b in patients from the south of Poland. PATIENTS AND METHODS: A total of 260 adult patients with CHC and HCV genotype 1b were treated with Peg-IFN alfa-2a or Peg-IFN alfa-2b with ribavirin for 48 weeks. Efficacy was assessed at 12 weeks (early virological response - EVR), 48 weeks (end-of-treatment response - ETR), and at 6 months (SVR). HCV-RNA, alanine transaminase (ALT), and other biochemical parameters were measured in serum at baseline and at 12, 48, and 72 weeks of therapy. RESULTS: HCV-RNA levels were 3.72 ±1.17 × 106 IU/ml at baseline and decreased significantly at 12 weeks (0.02 ±0.17 × 106 IU/ml); there were no differences between the group treated with Peg-INF alfa-2a and the group treated with Peg-INF alfa-2b. ALT was 94.1 ±7.6 IU/l at baseline and decreased significantly at 12 weeks (42.5 ±3.1 IU/l). The overall EVR, ETR, and SVR were achieved by 63.9%, 77.7%, and 48.1% of the patients, respectively. Tolerance of therapy was similar in both groups. CONCLUSIONS: Efficacy of Peg-IFN alfa-2a with ribavirin is not significantly different from that of Peg-IFN alfa-2b with ribavirin, and SVR was achieved in 48.3% and 44.3% of the patients, respectively. Our study confirms that the efficacy of treatment of patients with HCV genotype 1b from the southern region of Poland is similar to that observed in the overall Polish population.