M. avium is a ubiquitous type of bacteria found in water, mist, dust, soil and bird droppings. People usually become infected through contaminated food and water or, less often, by inhaling the organism. Healthy individuals can be infected but have no symptoms. In people who have AIDS or are otherwise immunocompromised, however, the organism can spread throughout the body, damaging tissues and causing fever, night sweats, weight loss, fatigue, or progressively severe diarrhea. In people with AIDS, M. avium infection usually occurs late in the course of the disease concurrent with low CD4+ T-cell counts.
Currently, any of three drugs-rifabutin, clarithromycin and azithromycin-are approved as standard therapy to prevent MAC in HIV-infected people with CD4+ T-cell counts below 50.
Once prevention measures have failed and someone develops MAC, however, treatment is more problematic. Patients require life-long maintenance therapy with multiple antibiotics-which can lead to the development of antibiotic resistance or drug intolerance-because symptoms return if treatment is stopped. Thus, researchers are interested in new treatment options.
IL-12 both enhances the immune system's ability to kill infected cells and induces the production of interferon gamma, a protein that helps control infections like MAC. IL-12 can stimulate interferon gamma even in the absence of T cells, a potential advantage when used to treat immunocompromised patients.
Through a series of experiments conducted in immunodeficient mice, Drs. Doherty
and Sher discovered that the combination of IL-12 and antibiotics has a
synergistic effect, working better than either IL-12 or drugs alone. Infected
mice were treated on alternate days for three sequential doses. After a two-day
rest period, the animals received another three doses on the same schedule.
Control animals were given saline alon
Contact: Laurie K. Doepel
NIH/National Institute of Allergy and Infectious Diseases