Immunological mechanisms of pentoxifylline in chronic heart failure
The Transplant Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester M23 9LT, UK
* Corresponding author. Tel: +44 161 291 5023, Fax: +44 161 291 5024, Email: james.fildes{at}manchester.ac.uk
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Abstract |
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The progressive syndrome of chronic heart failure (CHF) represents a common disease pathway that may be derived from a host of varying insults (including myocardial ischaemia and infarction, hypertension, viral infection, pregnancy, etc). Despite this multifarious aetiology, a common phenomena observed in CHF patients is elevated levels of tumour necrosis factor (TNF)-
. This has led to the widespread concept that TNF- is directly involved in the pathophysiology of CHF and as such, attempts have been made to inhibit TNF- production in this cohort. However, to date, there have been no clear beneficial effects from TNF- inhibition and indeed trials of direct anti-TNF therapy have provoked worsening of clinical outcomes. Conversely, a possible exception is pentoxifylline (PTX), a putative TNF- inhibitor with possible (but ill-defined) vasodilatory properties. Several small clinical trials assessing the use of PTX in CHF have suggested beneficial effects on multiple surrogate clinical markers. Interestingly, these trials failed to show a concordant effect on circulating TNF despite the clinical improvement, suggesting other key beneficial properties of this novel agent. This review article provides an insight into the potential beneficial mode of the action of PTX in CHF and calls for more investigation of this interesting agent.
Key Words: Tumour necrosis factor alpha • Chronic heart failure • Pentoxifylline • Immunomodulation
Received August 15, 2008; Revised December 1, 2008; Accepted December 8, 2008
See page 111 for the editorial comment on this article (doi:10.1093/eurjhf/hnf039)
Both authors have contributed equally to the manuscript.
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