This is the first study of chemokine concentrations in the aqueous humor of patients with acute anterior uveitis. The concentration of chemokines: IL-8, IP-10, MCP-1, RANTES and MIP-1 beta were significantly increased during the active stages of AU, and correlated with the clinical severity of the disease. These chemoattractant cytokines probably play a critical role in leucocyte recruitment in acute AU.
High concentrations of circulating 25-hydroxyvitamin D [25(OH)D] have been associated with elevated pancreatic cancer risk. As this is contrary to an expected inverse association between vitamin D status and cancer, we examined whether vitamin D binding protein (DBP), the primary carrier of vitamin D compounds in circulation, plays a role in this relationship. Prediagnostic serum DBP and 25(OH)D were studied in relation to risk of pancreatic cancer in a nested case-control study of 234 pancreatic cancer cases and 234 controls in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression, and statistical tests were two-sided. We found that DBP and 25(OH)D were correlated (r=0.27; p<0.0001), and DBP was inversely associated with pancreatic cancer risk (OR=0.66, 95% CI=0.39–1.12, for the highest vs. lowest quartile; p-trend=0.02). Importantly, this association appeared to have a threshold between quartiles 2–4 and quartile 1, and was primarily evident among men with concurrent high 25(OH)D concentrations (OR=0.33, 95% CI=0.16–0.70 for highest vs. lowest quartile; p-trend=0.002), with no association in men with lower serum 25(OH)D (OR=1.28, 95% CI=0.62–2.61 for highest vs. lowest quartile, p-trend 0.63, p-interaction= 0.01). Men with higher 25(OH)D concentrations and serum DBP below the median showed greatly elevated risk of pancreatic cancer (OR=5.01, 95% CI 2.33–10.78, for highest vs. lowest quartile; p-trend < 0.0001), while risk was weakly inversely associated with serum 25(OH)D when DBP concentrations were higher (p-interaction = 0.001). Taken together, our findings indicate that higher DBP concentrations may sequester more 25(OH)D and reduce free 25(OH)D bioavailability. Simultaneous examination of DBP and 25(OH)D may be important in determining the association of vitamin D with cancer risk.
The potential role of vitamin D in cancer prevention has generated substantial interest, and laboratory experiments indicate several anti-cancer properties for vitamin D compounds. Prospective studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, suggest an inverse association with colorectal cancer risk, but with some inconsistencies. Furthermore, the direct or indirect impact of the key transport protein, vitamin D binding protein (DBP), has not been examined. We conducted a prospective study of serum 25(OH)D and DBP concentrations and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, based on 476 colorectal cancer cases and 476 controls, matched on age, sex, race, and date of serum collection. All subjects underwent sigmoidoscopic screening at baseline and once during follow-up. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Circulating 25(OH)D was inversely associated with colorectal cancer (OR=0.60, 95% CI 0.38-0.94 for highest versus lowest quintile, p-trend 0.01). Adjusting for recognized colorectal cancer risk factors and accounting for seasonal vitamin D variation did not alter the findings. Neither circulating DBP nor the 25(OH)D:DBP molar ratio, a proxy for free circulating 25(OH)D, was associated with risk (OR=0.82, 95% CI 0.54-1.26, and OR=0.79, 95% CI 0.52-1.21, respectively), and DBP did not modify the 25(OH)D association. The current study eliminated confounding by colorectal cancer screening behavior, and supports an association between higher vitamin D status and substantially lower colorectal cancer risk, but does not indicate a direct or modifying role for DBP.
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