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TB treatment paradox: Mouse studies show body's own response helps TB bacteria survive
Date:6/28/2012

Inhibiting a key immune response in mice during initial multi-drug treatment for tuberculosis could paradoxically shorten treatment time for the highly contagious lung infection according to new research from Johns Hopkins Children's Center and the Center for TB Research.

Shorter duration of drug therapy is key, researchers say, to increase treatment compliance for the growing global health threat posed by the disease.

In experiments described in the June 27 issue of PLoS ONE, the Johns Hopkins investigators compared a group of TB-infected mice receiving standard TB treatment of rifampin, isoniazid and pyrazinamide with another group that received standard TB treatment plus etanercept, a drug used to inhibit a protein known as tumor necrosis factor alpha, or TNF-α, to prevent immune responses.

TB infection causes an immune response that notoriously includes production of TNF-α, which is critical for the formation of TB granulomas the hallmark tumors that form in the lungs and other parts of the body when the immune system tries to contain these bacteria. Paradoxically, this immune response is believed to wall off the bacteria, creating a sanctuary for "persistent" bacteria and, in turn, leading to the need for extended courses of treatment. Compliance with such treatment daily doses of antibiotics for six months or more is particularly challenging in the developing world and has fueled an epidemic of multi-drug resistant TB, the researchers say.

"New and shorter TB treatments are needed to stop this scourge globally, but current treatments largely target actively replicating bacteria, rather than slow-replicating, persistent TB bacteria," says Sanjay Jain, M.D., an infectious disease specialist at Hopkins Children's Center and the senior author of this study.

Aware that TB patients taking TNF-α inhibitors to treat other conditions such as rheumatoid arthritis and Crohn's disease can "w
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Contact: Kim Martin
kmartin7@jhmi.edu
410-502-9429
Johns Hopkins Medical Institutions
Source:Eurekalert

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