Circulating inflammatory cytokines and adipokines are associated with increased risk of Barrett's esophagus: a case-control study.

BACKGROUND & AIMS: Obesity is associated with Barrett's esophagus (BE) and with changes in circulating levels of adipokines (leptin and adiponectin) and cytokines. Although studies have reported that adipokines and inflammatory cytokines are necessary for the development of BE, their role is controversial. METHODS: We performed a case-control study; cases (n = 141) were patients who underwent esophagogastroduodenoscopy and were found to have BE, which was based on endoscopy and histology, and controls (n = 139) were primary care patients eligible for screening colonoscopies who agreed to undergo esophagogastroduodenoscopy. We examined the association between BE and circulating levels of adipokines and cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, and IL-12p70; tumor necrosis factor-α; and interferon-γ). Cases and controls were compared by calculating odds ratios (ORs) and 95% confidence intervals (CIs) and using unadjusted and multiple logistic regression, adjusting for age, sex, race, waist-hip ratio, use of proton pump inhibitors and nonsteroidal anti-inflammatory drugs, and Helicobacter pylori infection. RESULTS: The adjusted ORs for BE were 2.62 (95% CI, 1.0-6.8), 5.18 (95% CI, 1.7-15.7), and 8.02 (95% CI, 2.79-23.07) for the highest quintile vs the lowest quintile of levels of IL-12p70, IL-8, and leptin, respectively, but the OR was not significant for IL-6 (2.39; 95% CI, 0.84-6.79). The adjusted OR for BE was 0.14 for highest quintile of IL-10 compared with lowest quintile (95% CI, 0.05-0.35) and 0.03 for IL-1ß ≥ median vs none detected (95% CI, 0.006-0.13). Higher levels of IL-8 and leptin and lower levels of IL-10 and IL-1ß were associated with the presence of long-segment (≥3 cm) and short-segment BE. There were no differences between cases and controls in levels of interferon-γ, tumor necrosis factor-α, adiponectin, or insulin. CONCLUSIONS: BE is associated with circulating inflammatory cytokines and leptin and low levels of anti-inflammatory cytokines. These findings could partly explain the effect of obesity on BE.

Renal plasma flow: glomerular filtration rate relationships in man during direct renin inhibition with aliskiren.

We examined the relation between change in renal plasma flow (RPF) and change in glomerular filtration rate (GFR) in healthy humans on a low-salt diet during direct renin inhibition with aliskiren. We measured the renal hemodynamic response to acute dosing of 300mg aliskiren by mouth to 19 healthy normotensive subjects (age, 33+/-3 years; baseline RPF, 575+/-23; GFR, 138+/-14mL/min/1.73m(2)) on a low-sodium diet (10mmol/day). GFR and RPF were measured by the clearance of inulin and para-aminohippurate. There was a marked increase in average RPF (169+/-24mL/min/1.73m(2)) and a small rise in average GFR (1.4+/-5mL/min/1.73m(2)) from baseline in response to aliskiren. There was a clear correlation between the change in RPF and the change in GFR between subjects (r=0.65; P < .003). A substantial increase in RPF was accompanied by a rise in GFR. Dependence of GFR on RPF was identified in healthy humans after RPF rose significantly with aliskiren. The responsible mechanism likely involves intravascular oncotic pressure along the glomerular capillary resulting in greater surface area available for filtration.