Cytokines implicated in TB-induced HIV spike
Study shows importance of preventive therapy
Government researchers have shown in the past year that tuberculosis increases replication of HIV. A new study presented at the Fourth National Conference on Retroviruses and Opportunistic Infections in Washington, DC, has gone a step further and shown that this surge in HIV is associated with high levels of pro-inflammatory cytokines, such as interleukin-10, tumor necrosis-alpha, and interleukin-6.1 Finding ways to suppress these cytokines may be useful in treating co-infected patients and underscores the importance of early treatment for both diseases, they say.
"The delicate balance between pro-inflammatory and anti-inflammatory cytokines plays a major role in HIV replication induced by a common pathogen such as TB," says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, MD.
NIAID researchers, lead by Delia Goletti, MD, PhD, a former NIAID virologist now working in Rome found that when you add suppressive cytokines interleukin-10 and transforming growth factor-beta, TB-induced increases in HIV replication can be blocked. These cytokines appear to inhibit the virus by blocking the activity of pro-inflammatory cytokines and by diminishing the proliferations and activation of HIV-infected cells.
"Earlier, Goletti showed that for HIV-positive people who had TB, their viral load went up 20 fold during active TB," says Drew Weissman, MD, MPH, a senior fellow at NIAID. "Now we are trying to understand what regulates the virus and it appears that during TB disease cytokines are released and if you can inhibit them, you can regulate viral replication."
One potential blocker of pro-inflammatory cytokines is thalidomide, but so far the drug has not been shown to be effective, Weissman says.
How cytokines can be regulated in vivo is the next area to be researched, Goletti tells TB Monitor. "The next step in my research is to understand if TB-induced HIV replication is mediated by the endogenous release of pro-inflammatory cytokines and if anti-inflammatory cytokines secreted after TB stimulation may control TB-induced HIV replication."
The clinical implications of her research underscore the need for HIV-positive patients infected with TB to receive antiretroviral therapy as soon as possible. The findings also enforce the importance of preventive therapy for TB in co-infected patients "to prevent not only the bacterial disease but also the increase of HIV replication," she says.
Reference
1. Goletti D, et al. Exogenous and endogenous anti-inflammatory cytokines IL-10 and TGF-beta inhibit tuberculosis-induced HIV replication in CD8-depleted peripheral blood mononuclear cells from HIV-infected individuals. Presented at the Fourth National Conference on Retroviruses and Opportunistic Infections, Washington, DC, 1997. Abstract # 121.
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