Immune Therapy: Cytokines
Immune chemicals may hold hope for new treatments in HIV
January 2005 View PDF En
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The bleeding edge
Two cytokines are drawing increased interest from researchers for
their potential in treating HIV infection. These are interleukin-7
(IL-7) and interleukin-15 (IL-15).
Interleukin-7
A healthy adult will maintain a CD4+ cell count generally from 500–1,500.
What keeps cell counts from falling below 500 or from reproducing
out of control remains something of a mystery. When CD4+ cell counts
drop below normal ranges, other cells begin producing IL-7 (among
other things), which in turn stimulates CD4+ cells to reproduce
and causes the thymus (where new CD4+ cells come from) to produce
more CD4+ cells. Low CD4+ cell counts have been correlated to increases
in IL-7 levels in people with or without HIV (bone marrow transplant
patients, etc.). It’s theorized that the body produces more
IL-7 as CD4+ cell counts fall as a way to prompt the regeneration
of CD4+ cells to normal levels. For this reason it is believed to
be a potentially important HIV therapy.
The first human study of IL-7 is recruiting volunteers
in the setting of cancer. HIV researchers are watching this study
and will learn about dose, schedule and side effects that will be
further evaluated in HIV studies. While there is increasing interest
in using IL-7 for HIV, there are concerns about safety. IL-7 activates
HIV and particularly a very aggressive form of HIV, called syncitia
inducing (SI) or R4-dependent virus. It’s possible that this
concern could be lessened by giving IL-7 with anti-HIV medications.
Some research in animals suggest that short-term activation of HIV
by IL-7 might be a good thing as it may decrease the reservoir of
HIV lurking in resting cells. The major barrier to moving this research
forward is that no company committed to HIV research currently makes
a form of quality controlled IL-7 suitable for large human studies.
Interleukin-15
Interleukin-15 (IL-15) appears to preferentially enhance CD8+ cell
number, function and survival in animal and lab studies. These cells
are important in cell-to-cell killing of virally infected cells.
While IL-2 stimulates CD4+ cells to reproduce, IL-15 stimulates
CD8+ cells. Also, IL-15 appears to inhibit cell death caused by
activation. Immune activation and a cascade of activation-induced
cell death are increasingly believed to be part of the immune dysfunction
of HIV disease (the “sink and drain” notion that HIV
simply kills billions of cells each day is no longer widely held).
Increases in IL-15 levels have been associated with better control
of HIV infection, though which is the cause and which is the effect
have not been clearly determined. An IL-15 study for treating HIV
has been in development for years and never materialized. The major
barrier to moving this research forward is that the company who
owns IL-15 (Amgen) is not committed to HIV research.
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