interleukin-8 and Erectile-Dysfunction

Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNF α and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis.

Topics: Apolipoprotein B-100; Atherosclerosis; Endocytosis; Erectile Dysfunction; Fatty Liver; Female; Fibrinolysis; Humans; Hydrogen Peroxide; Inflammation; Interleukin-8; Lipoproteins, LDL; Macrophages; Male; Oxygen; Peroxidase; Pulmonary Disease, Chronic Obstructive; Renal Dialysis; Sleep Wake Disorders; Tumor Necrosis Factor-alpha

We investigated changes in serum biomarkers of vascular function after short-term, continuous sildenafil dosing in men with type 2 diabetes with erectile dysfunction.. Men with erectile dysfunction associated with type 2 diabetes mellitus were randomized to receive continuous, daily sildenafil (50 mg for 1 week run-in and 100 mg for 3 weeks) (148), or placebo (144) for 4 weeks (phase I) and then sildenafil (25, 50 or 100 mg) on demand for 12 weeks (phase II). Blood draws at baseline and after phases I and II were analyzed for cyclic guanosine monophosphate (endothelial function marker), 8-isoprostane (oxidative stress marker), and interleukin-6 and interleukin-8 (inflammatory cytokines). Primary and secondary erectile function outcome variables were affirmative responses on Sexual Encounter Profile question 3 (ability to maintain erection sufficient for sexual intercourse) and Erection Hardness Score, respectively.. Serum cyclic guanosine monophosphate levels were increased in the sildenafil group relative to the placebo group at 4 (p <0.01) and 16 (p <0.05) weeks, correlating with affirmative responses to Sexual Encounter Profile question 3 at the 4-week interval only (p <0.05). Serum 8-isoprostane levels were decreased to a nonsignificant degree in the sildenafil group at 4 weeks with no further change at 16 weeks, whereas interleukin-6 and interleukin-8 levels were unchanged at either interval, and these levels were unassociated with erectile function outcomes.. These data suggest that short-term, continuous sildenafil treatment causes systemic endothelial function to be enhanced and remain so for a duration after its discontinuation. However, they do not indicate any influence of this treatment on systemic oxidative stress or inflammation, or an effect on long-term erectile function improvement.

Topics: Adult; Aged; Biomarkers; Cyclic GMP; Diabetes Complications; Diabetes Mellitus, Type 2; Dinoprost; Endothelium, Vascular; Erectile Dysfunction; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Oxidative Stress; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome

Patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) show a high prevalence of erectile dysfunction (ED). Although the underlying pathogenesis is still unknown, endothelial dysfunction, induced by inflammatory cytokines, chemokines, and adhesion molecules, has been proposed as a possible mechanism. The aim of this study was to assess whether OSAHS is associated with activation of the inflammatory cytokine system in patients with ED compared to the matched OSAHS patients with normal sexual function. Thirty-one patients with severe OSAHS and ED were included. Fifteen patients with severe OSAHS and without ED served as controls. Serum concentrations of high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-a), interleukin-6 (IL-6), interleukin-8 (IL-8), and adiponectin were measured after the diagnostic polysomnography. We found that hsCRP levels were significantly elevated in OSAHS patients with ED compared to controls. Similarly, TNF-a levels, IL-6, and IL-8 were elevated in OSAHS patients with ED compared to controls. Serum adiponectin levels were lower in OSAHS-ED patients, but the difference did not reach statistical significance. The presence of ED in patients with severe OSAHS is associated with elevated levels of inflammatory markers, underlining a possible involvement of endothelial dysfunction in the pathogenesis of ED.

Topics: Adiponectin; Adult; Body Mass Index; C-Reactive Protein; Cytokines; Erectile Dysfunction; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Surveys and Questionnaires; Tumor Necrosis Factor-alpha