Anti-TNF Therapy Reactivates Latent Tuberculosis

Mathematical model shows low levels of soluble TNF are essential for controlling tuberculosis infections

MONDAY, Oct. 29 (HealthDay News) -- Anti-tumor necrosis factor (TNF) therapy can reactivate latent tuberculosis infections by decreasing the bioavailability of TNF in granulomatous tissue, according to a report published in the October issue of PLoS -- Computational Biology.

Simeone Marino, Ph.D., of the University of Michigan Medical School in Ann Arbor, and colleagues used a mathematical model to study the effects of anti-TNF therapy in virtual clinical trials that simulated two commonly used therapies, anti-TNF antibody and TNF receptor fusion, to identify the mechanism behind tuberculosis reactivation.

The researchers found that the low bioavailability of TNF after anti-TNF therapy was primarily responsible for the reactivation of latent infections. They also found that soluble TNF -- even at extremely low levels -- is necessary for controlling the infections. Their model predicted that 0.2 percent of total TNF needs to be released in soluble form to control acute infections and maintain latency.

"Our study suggests that a TNF-modulating agent could be developed that could balance the requirement for reduction of inflammation with the necessity to maintain resistance to infection and microbial diseases," the authors conclude. "Alternatively, the dose and timing of anti-TNF therapy could be modified. Anti-TNF therapy will likely lead to numerous incidents of primary tuberculosis if used in areas where exposure is likely."

One study author has received grant funding from Amgen, the makers of etanercept.

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