How are cytokines activated in heart failure?

In the dilated and failing heart, elevated LV end-diastolic wall stress causes myocardial expression of cytokines, which directly or indirectly influence LV contractile performance and remodeling [22]. Due to poor diffusion of cytokines into the coronary effluent, the contribution of this myocardial production to the raised plasma levels is probably limited. Raised plasma levels of cytokines in heart failure are therefore more likely the result of extramyocardial production because of altered tissue perfusion and tissue hypoxia possibly modulated by bacterial endotoxin release from the gut.