Emerging role for TNF-α in erectile dysfunction

J Sex Med. 2010 Dec;7(12):3823-34. doi: 10.1111/j.1743-6109.2010.01762.x.


Introduction: A role for cytokines in the pathophysiology of erectile dysfunction (ED) has emerged. Cytokines induce genes that synthesize other peptides in the cytokine family and several mediators, such as prostanoids, leukotrienes, nitric oxide, bradykinin, reactive oxygen species, and platelet-activating factor, all of which can affect vascular function. Consistent with the fact that the cavernosal tissue is a complex extension of the vasculature, risk factors that affect the vasculature have been shown to affect cavernosal function as well. Accordingly, the penile tissue has been recognized as an early sentinel for atherosclerosis that underlies coronary artery disease and cardiovascular diseases (CVD).

Aim: To review the literature pertaining to the role of tumor necrosis factor-alpha (TNF-α) in ED.

Methods: PubMed search for pertinent publications on the role of cytokines, particularly TNF-α, in CVD and ED.

Main outcome measures: Clinical and experimental evidence demonstrates that TNF-α may play a role in ED.

Results: TNF-α has been shown to play an important role in CVD, mainly due to its direct effects on the vasculature. In addition, high levels of TNF-α were demonstrated in patients with ED. In this review, we present a short description of the physiology of erection and the cytokine network. We focus on vascular actions of TNF-α that support a role for this cytokine as a potential candidate in the pathophysiology of ED, particularly in the context of CVD. A brief overview of its discovery, mechanisms of synthesis, receptors, and its main actions on the systemic and penile vasculature is also presented.

Conclusions: Considering that ED results from a systemic arterial defect not only confined to the penile vasculature, implication of TNF-α in the pathophysiology of ED offers a humoral linking between CVD and ED.

Publication types

  • Review

MeSH terms

  • Coronary Artery Disease / physiopathology
  • Cytokines / physiology
  • Endothelium, Vascular / physiopathology
  • Erectile Dysfunction / physiopathology*
  • Fas-Associated Death Domain Protein / physiology
  • Humans
  • Inflammation / physiopathology
  • Male
  • Penile Erection / physiology
  • Receptors, Tumor Necrosis Factor / physiology
  • Signal Transduction
  • TNF Receptor-Associated Death Domain Protein / physiology
  • Tumor Necrosis Factor-alpha / physiology*
  • rho-Associated Kinases / physiology


  • Cytokines
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Receptors, Tumor Necrosis Factor
  • TNF Receptor-Associated Death Domain Protein
  • Tumor Necrosis Factor-alpha
  • rho-Associated Kinases