What causes low Tumor Necrosis Factor-alpha (TNF-alpha) levels in men?

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Last updated: March 7, 2025View editorial policy

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From the Guidelines

Low TNF-alpha levels in men are most commonly caused by the use of TNF inhibitors, such as adalimumab, infliximab, and etanercept, as well as corticosteroids like prednisone, which are used to treat autoimmune conditions and can suppress TNF-alpha production. These medications are often prescribed for conditions like rheumatoid arthritis, psoriasis, and Crohn's disease, and can significantly reduce TNF-alpha levels in the body 1. Other factors that may contribute to low TNF-alpha levels include genetic variations, lifestyle factors such as regular intense exercise and caloric restriction, and underlying health conditions like immunodeficiencies and certain cancers.

Medications that Suppress TNF-alpha

  • TNF inhibitors: adalimumab (Humira), infliximab (Remicade), and etanercept (Enbrel) 1
  • Corticosteroids: prednisone (typically 5-60mg daily)
  • Non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen

Lifestyle Factors that May Contribute to Low TNF-alpha

  • Regular intense exercise
  • Caloric restriction
  • Adequate sleep

Health Conditions Associated with Reduced TNF-alpha

  • Certain immunodeficiencies
  • Some cancers
  • Specific genetic polymorphisms affecting cytokine production It is essential to note that low TNF-alpha levels can impair immune function against infections and cancer surveillance, and consulting with an immunologist or rheumatologist is recommended for proper evaluation and management if concerned about low TNF-alpha levels.

From the Research

Causes of Low Tumor Necrosis Factor-alpha (TNF-alpha) Levels in Men

There are several potential causes of low TNF-alpha levels in men, including:

  • Age: A study published in 2017 2 found that young men had higher serum concentrations of soluble TNF-alpha receptor 1 (STNFR1) than middle-aged men, suggesting that natural inhibitors of TNF-alpha may decline with age.
  • Exercise: The same study found that acute eccentric exercise did not significantly affect TNF-alpha levels in young or middle-aged men, but did cause changes in STNFR1 and STNFR2 concentrations.
  • Thyroid function: A study published in 2002 3 found that patients with hypothyroidism had higher serum concentrations of TNF-alpha than healthy controls, but normalization of thyroid function did not significantly modify TNF-alpha levels.
  • Prostatic secretions: A study published in 2000 4 found that men with chronic prostatitis had higher levels of TNF-alpha in their prostatic secretions than healthy men or men with benign prostatic hyperplasia.

Potential Factors Influencing TNF-alpha Levels

Other factors that may influence TNF-alpha levels in men include:

  • Autoimmune diseases: Studies have shown that TNF-alpha is elevated in many autoimmune diseases, and that anti-TNF-alpha therapies can be effective in treating these conditions 5, 6.
  • Inflammation: TNF-alpha is a proinflammatory cytokine, and its levels may be influenced by the presence or absence of inflammation in the body.
  • Hormonal changes: Hormonal changes, such as those that occur with aging or thyroid dysfunction, may also affect TNF-alpha levels.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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