The roles of cytokines in heart failure. Cardiac stressors that initiate and exacerbate cardiac dysfunction evoke leucocyte activation in the heart with cytokine production and release. The associated skeletal muscle deconditioning up-regulates the same cytokines, albeit to a lesser extent. TNF and IL-1β, through IL-6 promote CRP production in the liver. The release of this acute phase reactant appears to be a composite biomarker of the inflammatory cascade activated by heart failure and its levels predict outcome. The inset shows the targeting of cytokines with mixed effects. HF, heart failure; HHF, hospitalization from HF; hsCRP, highly sensitive C-reactive protein.