Immune Therapy: Cytokines

Immune chemicals may hold hope for new treatments in HIV

January 2005     View PDF     En español

Tried and failed, and tried again?

Several cytokines have been looked at in the context of HIV. Interferon-gamma enhances the function of cells that control mycobacterial infections, including tuberculosis and MAC. It has been studied together with anti-TB treatment in people with TB and HIV. It is also being looked at as an adjunctive therapy to enhance vaccine effects. Early studies suggest that low doses of interferon-gamma may control HIV whereas high doses may promote HIV replication. Interferon-gamma, however, is also associated with cell activation, which isn’t necessarily a good thing. Over the years, increased interferon-gamma levels have alternately been described as both a good thing and a bad thing.

This point is important when considering the challenges of researching cytokines. In the body, cells are producing these chemicals at very, very small—nanomolar—concentrations and together with other cytokines. The combination of cytokines, in varying concentrations, elicits different immune responses. At low doses IL-2 preferentially stimulates natural killer cells, while at higher doses, delivered intermittently, it stimulates CD4+ cells to reproduce. When IL-2 is given at high dose daily it produces no appreciable effect on CD4+ cell count. When it is given for five days every eight weeks, the effect is profound and pronounced The challenge with cytokine research is not merely to understand the various biologic functions of the cytokine, but also how best to give the therapy to achieve the desired responses.

Interleukin-12
Interleukin-12 (IL-12) was researched in the early 1990s because it’s believed to enhance cellular immune responses (the type of responses associated with killing HIV-infected cells, as opposed to killing free virus in blood). Results from small studies suggest it had no effect on either HIV levels or CD4+ cell counts at doses that were tolerable. However, dosing and schedules of doses may not have been fully explored to truly understand the potential of this therapy.

Granulocyte macrophage colony stimulation factor
Granulocyte macrophage colony stimulation factor (GM-CSF) was evaluated in a large study to see if adding it to anti-HIV therapy would decrease risks for opportunistic infections among people with more advanced HIV disease. While there were some interesting observations of decreases of specific bacterial infections among those receiving GM-CSF compared to placebo, the differences were not significant overall.

Interleukin-10
Interleukin-10 (IL-10) is an immune suppressive cytokine that suppressed HIV replication in test tubes. One study in people showed no impact on HIV replication, positive or negative when IL-10 was given at 1, 4 or 8µg/kg daily compared to placebo. Another study suggested that IL-10 therapy may decrease HIV levels.

Interleukin-4
Interleukin-4 (IL-4) has been researched for activity against the AIDS-related cancer Kaposi’s sarcoma (KS) and its impact on HIV was monitored. At a dose of 1µg/kg daily, IL-4 had no effect on HIV levels and little to no impact on KS.

These are a handful of cytokines that have been studied in the setting of HIV. While they failed to show benefit, it may be that at different doses, given intermittently as opposed to daily, or combined with other cytokines, they will one day be researched again and show promise.

The bleeding edge

LAST      NEXT

Conclusion