Immune Boosting Drug Worsens Tuberculosis in Mice

According to scientists from the National Institutes of Health, an experimental drug that boosts production of the immune system protein interferon worsens tuberculosis in mice.

The drug acts indirectly by drawing certain immune cells, in which Mycobacterium tuberculosis (M.tb) bacteria thrive, to the lungs. Most people infected with M.tb do not develop active tuberculosis.

Instead, the infection can remains dormant for decade, but 10 percent of people with latent infection do go on to develop active disease. Some causes for reactivation include aging or other conditions that lower immunity.


“Although our research was conducted in mice, our combined findings suggest that reactivation of tuberculosis should be considered as a potential side effect if compounds that boost type I interferon production, like the one used in this study, are tested in people who may be infected with M.tb,” says Alan Sher, Ph.D., of the National Institute of Allergy and Infectious Diseases (NIAID), NIH, who led the team of scientists.

Dr. Sher and his colleagues studied the effects of an experimental drug called poly-ICLC on immune responses to tuberculosis infection. Poly-ICLC stimulates the body to produce an immune system protein called type I interferon (type I IFN) that has the ability to interfere with viral infections.

In mouse studies, poly-ICLC protected the animals from viruses that can cause lethal infections, including pandemic influenza. It has also been shown to improve the effects of several experimental vaccines when tested in animals. Poly-ICLC also is being tested in multiple human clinical trials as a possible cancer treatment when combined with cancer vaccines.

Earlier research into the effects of type I IFN on bacterial infections produced mixed results. Some studies showed that giving IFN to mice with non-tuberculous mycobacterial infections lowered the amount of bacteria in their bodies, but in another studies, naturally occurring IFN appeared to promote rather than limit the growth of bacteria in mice infected with M.tb.

To sort things out, NIAID investigator Lis R.V. Antonelli, Ph.D., dropped poly-ICLC into the noses of mice that had been infected with M.tb. The mice were infected either one day earlier to mimic an acute tuberculosis infection, or four months earlier to make a chronic tuberculosis infection. The infected mice were then compared with untreated mice with tuberculosis. All the mice treated with poly-ICLC developed severe lung tissue damage.

Also, levels of M.tb in their lungs were 100 times greater than in M.tb-infected mice that did not receive poly-ICLC.

Next, Dr. Antonelli performed a few more experiments to see what kind of immune system cell was involved in speeding up the disease in poly-ICLC-treated mice. In the treated group of mice, the scientists found a fourfold increase in immune cells called macrophages. 

 In most infectious diseases, macrophages are drawn to the site of infection and help defend the host against disease, but when type I IFN production was elevated by poly-ICLC treatment, the surge in macrophages to the M.tb-infected lung actually harmed the host.

Researchers are currently testing the relevance of these findings to humans by determining whether under certain conditions type I IFN promotes the growth of M.tb in human macrophages. Such research could also provide important clues to how and under what conditions dormant tuberculosis is reactivated

 From:- http://techcombo.com/2010/06/30/immune-boosting-drug-worsens-tuberculosis-in-mice-123/