No abstract

The pro-inflammatory cytokines IL-8 and MCP-1 are increased in the vitreous fluid of PDR patients without an increase in the anti-inflammatory cytokine IL-10. In addition, both IL-8 and MCP-1 intra-vitreous levels correlated with PDR activity, thus suggesting that these cytokines may be pathogenically important in PDR.

OBJECTIVE -To evaluate the intravitreous concentration of vascular cell adhesion molecule (VCAM)-1 in diabetic patients with proliferative diabetic retinopathy (PDR) and the relationship of VCAM-1 with vascular endothelial growth factor (VEGF).RESEARCH DESIGN AND METHODS -Serum and vitreous fluid samples were obtained simultaneously at the onset of vitrectomy from 20 diabetic patients with PDR and 20 nondiabetic control subjects with nonproliferative ocular disease. Both groups were matched by serum levels of VCAM-1 and VEGF. VCAM-1 and VEGF were determined by enzyme-linked immunosorbent assay. Statistics were determined using the Mann-Whitney U test and Spearman's rank correlation test.RESULTS -The intravitreous concentration of VCAM-1 was significantly elevated in diabetic patients with PDR compared with control subjects (26 ng/ml [19 -118] vs. 22 ng/ml [20 -47], P Ͻ 0.05). A direct correlation between VCAM-1 and total vitreous proteins was detected in diabetic patients (r ϭ 0.64, P ϭ 0.003), but not in control subjects. After adjusting for total intravitreous proteins, VCAM-1 was significantly lower in diabetic patients with PDR than in control subjects (8.2 ng/ml [4 -31.4] vs. 43.1 ng/ml [9.7-100], P Ͻ 0.001). Intravitreous VEGF concentrations were higher in patients with PDR than in control subjects in absolute terms (1.34 ng/ml [0.16 -6.22] vs. 0.009 ng/ml [0.009 -0.044], P Ͻ 0.0001) and after correcting for total vitreal proteins (0.33 ng/ml [0.01-2.3] vs. 0.013 ng/ml [0.003-0.035], P ϭ 0.0001). Finally, the vitreous ratio of VCAM-1 to proteins correlated with the vitreous ratio of VEGF to proteins in both diabetic patients (r ϭ 0.74, P ϭ 0.001) and control subjects (r ϭ 0.84, P ϭ 0.005).CONCLUSIONS -The low proportion of VCAM-1 in relation to total vitreal proteins observed in diabetic patients with PDR suggests that VCAM-1 is quenched by diabetic retina. In addition, the direct correlation detected between VCAM-1 and VEGF suggests that cellular adhesion and neovascularization may be linked processes. Diabetes Care 24:516 -521, 2001P roliferative diabetic retinopathy (PDR) is characterized by extensive neovascularization and vessel intrusion into the vitreous body, with subsequent bleeding and scarring surrounding new vessels, leading to severe visual impairment. Ischemic areas of the retina seem to be essential stimuli for the angiogenic process mediated by specific growth factors. This includes the expression of vascular endothelial growth factor (VEGF) by retinal glial cells (1) and vascular endothelial cells (2). It is thought that capillary occlusion by increased adhesion of leukocytes and macrophages to the endothelium has a crucial role in the process of retinal ischemia (3). In addition, monocytes exposed to glycated collagen show increased adhesiveness (4), and several studies indicate that circulating leukocytes are activated in diabetic patients (5,6).Vascular cell adhesion molecule (VCAM)-1, a member of the immunoglobulin supergene family of cellular adhesion molecules, is involved in the re...

Although the activity of the nitric oxide pathway is increased in patients with cirrhosis and might contribute to the hemodynamic alteration, other factors are involved. Interleukin-6, possibly through nitric oxide-independent mechanisms, also might play a role in the vasodilatation of cirrhosis and the pathogenesis of hepatic encephalopathy.

Sepsis is the most important cause of mortality in the Intesive Care Units. At present, sepsis is understood to be the inflammatory response of the host to infection, rather than a direct effect of microbial aggression. From the clinical standpoint, this inflammatory response is known as systemic inflammatory response syndrome (SIRS). Pathophysiologically, SIRS is characterized by the activation of several groups of cell (monocytes/macrophages, PMNs, and endo-thelial cells) and by the release of inflammatory mediators (cytokines and others). Tumor necrosis factor (TNF) is the first cytokine released by endotoxin action over monocyte/macrophage. TNF secretion, modulated by interferon gamma (IFNγ) and interleukin 10 (IL-10), is followed by release of other cytokines such as interleukins (IL) (IL-1, IL-6 and IL-8). These mediators are able to act over hemostasis activating the extrinsic pathway through tissue factor expression. The action of the mediators over endothelial cells induces an increase in plasminogen activator inhibitor type 1 (PAI-1) levels with inhibition of fibrinolysis. Both coagulation activation and fibrinolysis blockage result in fibrin deposit in the microvascular system. The complexity of the mechanisms implicated in systemic inflammatory response make a general rule so difficult to establish, because patient response is highly individualized and it is not possible to know which moment of this dynamic process is being analyzed.