Heart failure as an inflammatory condition: potential role for androgens as immune modulators.
Heart failure has traditionally been considered a disease of the myocardium, with symptoms arising from altered haemodynamics. However, it is now recognised that, in addition to marked neuroendocrine disturbance, there is perturbation of cytokine expression in patients with heart failure, resulting in an inflammatory imbalance. This not only influences symptoms, but also plays a central role in the underlying pathophysiological processes of heart failure, leading to disease progression and poorer prognosis. Recognition of the influence of cytokines, in particular tumour necrosis factor, has opened a new avenue for potential therapies for heart failure. Current approaches involve immunomodulation, aimed at suppressing tumour necrosis factor. We suggest that androgens may potentially offer a superior therapeutic strategy by their well-recognised non-specific immunosuppressive and anti-inflammatory effects. Studies of cell lines, human mononuclear cells and animals in vivo have demonstrated the 'anti-cytokine' actions of androgens, and we have found a similar action in whole blood from patients with heart failure. These effects, along with the anabolic action of these agents, make androgens an attractive potential option for treatment of patients with heart failure.
Pugh
Peter J
PJ
Department of Cardiology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK.
Jones
Richard D
RD
Jones
T Hugh
TH
Channer
Kevin S
KS
D000728:Androgens / Q000627:therapeutic use*; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D018836:Inflammation Mediators / Q000032:analysis*; D008297:Male; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
D000728:Androgens; D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators