Interleukin-6 as a central mediator of cardiovascular risk associated with chronic inflammation, smoking, diabetes, and visceral obesity: down-regulation with essential fatty acids, ethanol and pentoxifylline.

Increased plasma levels of fibrinogen and C-reactive protein (CRP), as well as leukocytosis, are now established as risk factors for the thromboembolic complications of vascular disease. Chronic inflammation or infection associated with an acute-phase response--notably, periodontal disease and smoking-induced lung damage--are likewise known to increase cardiovascular risk. A common etiologic factor in these conditions may be interleukin-6 (IL-6), acting on hepatocytes to induce acute-phase reactants that increase blood viscosity and promote thrombus formation. Recent evidence that hypertrophied adipocytes release IL-6, and that hyperglycemia evokes IL-6 production by endothelium, may explain why plasma fibrinogen is increased in visceral obesity and poorly controlled diabetes. IL-6 is released by a range of tissues in response to stimulation by the monocyte-derived cytokines interleukin-1 and tumor necrosis factor; by suppressing production of these cytokines, fish oil, alpha-linolenic acid, and pentoxifylline can reduce IL-6 synthesis. Moderate ethanol consumption, as well as sex-hormone replacement, also appear to inhibit IL-6 production or activity. These practical protective measures may be of particular value to patients with pre-existing atheroma and elevated plasma levels of acute-phase reactants. Since IL-6 plays a crucial physiological role in osteoclast generation and activation, these measures may also aid preservation of bone density.