Fauci Lab Presents New Data on AIDS Pathogenesis, Treatment at Retroviruses Conference

Robert Walker, et al. Effects of TNF-alpha antagonists thalidomide and monoclonal
anti-TNF antibody (cA2) on reducing IL-2-associated toxicities: a randomized, controlled trial.
Session 8, Abstract 36. Thursday, 10:30 a.m.
4. IL-10 Study: Transient Reduction in Viral Load Due to Altered Cytokine
Environment and Co-Receptor Expression
In cell culture experiments conducted over the past decade, LIR scientists have
demonstrated that certain cytokines normally secreted by immune system cells, such as tumor
necrosis factor-alpha and interleukin-6, can boost the replication of HIV. Other cytokines such
as interleukin-10 inhibit HIV replication, in part by blocking the activity of TNF-alpha and IL-6.
These in vitro experiments have shown that HIV replication is regulated by a delicate
balance between inductive and suppressive cytokines. Altering this balance can dramatically
influence HIV replication in the test tube and perhaps, new research suggests, in the body as
well.
In a phase I clinical trial at NIAID, Drew Weissman, M.D., Ph.D., and his colleagues
administered a single, low dose of IL-10 to 11 HIV-infected people and found that their
bloodstream levels of HIV dropped by about 70 percent. Virus levels were lowest
approximately 12 hours following injection, and returned to baseline about 24 hours after the
IL-10 injection. The investigators noted no adverse events associated with the injection.
Two observations may help explain the transient drop in virus levels associated with
IL-10 injections, the researchers suggest. First, following IL-10 injection, patients' immune
system cells made considerably less of the inductive cytokines such as TNF-alpha known to
boost HIV replication. Second, the patients' CD4+ T cells expressed fewer of the co-receptors
that are needed by HIV to bind to and enter these cells.
"Our findings fortify the concept that the body's own complex network of cytokines plays
a pivotal role in determining the net rate of viral replication in an HIV-infected individual," says
Dr. Weissman. "It may prove possible to manipulate this network to therapeutic advantage."
Drew Weissman, et al. Interleukin-10 decreases HIV plasma viral load: results of a
phase I clinical trial. Session 8, Abstract 37. Thursday, 11:30 a.m.
5. IL-10, TGF-Beta Inhibit TB-Induced HIV Replication
Last year, LIR scientists demonstrated that active TB infection boosts HIV replication in
HIV-infected people (see Journal of Immunology 1996;157:1271-78). This observation helped
explain why HIV-infected people with active TB have a poorer prognosis that HIV-infected
people without TB. The researchers also found that the TB organism and TB-derived proteins
increase HIV replication in the test tube when added to cells taken from HIV-infected patients.
New in vitro observations, to be presented by Delia Goletti, M.D., Ph.D., formerly of LIR
and now working in Italy, show that TB-induced increases in HIV replication are associated with
high levels of pro-inflammatory cytokines such as interleuk'n-1, tumor necrosis-alpha and
interleukin-6.

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