C-reactive protein is elevated in the offspring of parents with essential hypertension.

BACKGROUND: Hypertension is a risk factor for cardiovascular disease (CVD). Studies in adults have shown that high sensitivity C-reactive protein (CRP) levels are associated with increased risk of CVD and essential hypertension (EHT). Genetic background is widely accepted as a risk factor for CVD. The aim of the present study was to analyse the association of high sensitivity CRP levels with other cardiovascular risk factors in children and young adults with at least one parent with EHT. METHODS: Fifty one healthy children and young adults (28 boys) with at least one parent with hypertension and 69 (41 boys) whose parents did not have hypertension were recruited prospectively from primary care centres. High sensitivity CRP, fasting lipid profile, blood pressure (BP) and anthropometric variables were obtained for all participants. RESULTS: CRP values were higher in the study group than in controls (logCRP mean difference: -0.69; 95% confidence interval: -1.05 to -0.33), even when differences were adjusted for age, gender, body mass index (BMI) and triglyceride levels (p = 0.01). No differences were observed in BP values between groups. In the study group, 35.3% of the participants had a CRP level > or =1 mg/l compared to 14.5% in the control group (p = 0.009). CRP showed a significant correlation with body weight (rho = 0.28, p = 0.04), BMI (rho = 0.32; p = 0.02) and ponderosity index (rho = 0.28; p<0.05). CONCLUSIONS: CRP is significantly higher in the offspring of parents with EHT. A significant positive relationship exists between BMI and serum CRP levels in this high risk group of children and young adults.

In vivo interleukin-6 protects neutrophils from apoptosis in osteomyelitis.

Polymorphonuclear neutrophils are critical for resolution of bacterial infections. In tissues, most of the neutrophils quickly die through apoptosis. Using propidium iodide DNA staining and DNA gel electrophoresis, we found that spontaneous apoptosis of neutrophils from patients suffering osteomyelitis (n = 52) was significantly decreased in relation to control neutrophils (n = 20) (40.2% +/- 25.2% versus 54.5% +/- 23.5%; P < 0.03). Incubation of neutrophils from normal volunteers with sera from patients with osteomyelitis reduced apoptosis from 79.1% +/- 14.8% in control sera to 62.2% +/- 18.7% in osteomyelitis sera. A significant increase of serum interleukin-6 (IL-6) and IL-1alpha was found in osteomyelitis (IL-6, 8.8 +/- 11.9 pg/ml versus 1.8 +/- 1.2 pg/ml in controls [P < 0.004]; IL-1alpha, 3.8 +/- 6.4 pg/ml versus 1.0 +/- 2.2 pg/ml in controls [P < 0.02]). No differences in the levels of other cytokines, such as tumor necrosis factor alpha, were found. There was an inverse correlation between IL-6 levels and neutrophil apoptosis (r = -0.855; P < 0.007), but this was not the case for other cytokines. The antiapoptotic effect of the osteomyelitis sera was reversed with anti-IL-6 antibodies (P < 0.03) and was reproduced with recombinant human IL-6 (P < 0.001). The longer life span of neutrophils in osteomyelitis induced by IL-6 could contribute to the tissue damage that occurs in these chronic bone infections.

High serum tumor necrosis factor-alpha levels are associated with lack of response to infliximab in fistulizing Crohn's disease.

OBJECTIVES: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor-alpha (anti-TNF-alpha), has been effective in the treatment of patients with active Crohn's disease and with fistulas. We investigated the effect of infliximab on circulating cytokines and acute phase proteins in patients with fistulas to determine the clinical response to anti-TNF-alpha. METHODS: A total of 36 patients with fistulizing Crohn's disease were selected for study. Serum from patients was drawn before the infusion on day 0 and at wk 2, 4, 6, 8, and 10 after completion of treatment. Circulating concentrations of TNF-alpha, interleukin-1beta (IL-1beta), and IL-6 were measured by ELISA. The functional activity of circulating TNF-alpha was assessed by the WEHI 164 TNF-alpha bioassay. Acute phase proteins were also determined. RESULTS: Elevated TNF-alpha, IL-1beta, IL-6, and acute phase proteins were observed in patients with Crohn's disease. Of the patients with fistulas, 22 (61.1%) responded to treatment. Before receiving infliximab, higher levels of serum TNF-alpha were found in patients who did not respond to infliximab compared with those who did (median interquartile range 26, 0-245 pg/ml; n = 14 vs 0, 0-22 pg/ml, n = 22). Patients showed no change in circulating levels of TNF-alpha during the course of the study. CONCLUSIONS: This treatment produces a clinical improvement in about two-thirds of CD patients with fistulas. The circulating levels of TNF-alpha are associated with the response to infliximab and could help to identify patients who would benefit from anti-TNF-alpha treatment.