Thalidomide, Melatonin, DHEA, TNF, and IL-2
I think this will not only be interesting to this group, but it may actually
prove
beneficial. Nov. 11, I posted "Thalidomide and DHEA" to relavent
newsgroups. (That post is added to the end of this one.) In my post of the
11th., I said I think thalidomide works, because it mimics the natural
hormone, melatonin. Today I was reading a post in which it was stated that
thalidomide is used in AIDS because it reduces TNF. This was in "Re:
Thalidomide?????," today:
"jscutero at panix.com (James Scutero) wrote:
>Thalidomide is used because it lowers high levels of TNF alpha, an
>inflammatory cytokine(protein). I don't know how it does this,
>but I do know that thalidomide is neurotoxic and can exacerbate
>peripheral neuropathy, along with causing other toxicities."
I had developed my hypothesis of how thalidomide works when it was being
posted in these groups that it might help with the wasting syndrome. The
11th., I finally posted it. The quoted material above made me wonder if
melatonin would reduce TNF alpha, since thalidomide does. I did not expect
to find anything, but melatonin is known to affect TNF alpha production and
augment interleukin-2 effects on lymphocyte proliferation. The following
quotations are studies in cancer patients, in which TNF and IL-2 are being
considered as therapies. However, these quotations speak for themselves,
for AIDS groups.
Stefano, A Di and Paulesu L "Inhibitory Effect of Melatonin on Production of
IFN Gamma or TNF alpha in Peripheral Blood Mononuclear Cells of Some
Blood Donors," J Pineal Res 1994; 17: 164
"Melatonin at physiological concentrations fails to induce production of IFN
or TNF by PBMC in culture but causes a dose-related inhibition of
production of both cytokines if the PBMC are stimulated with
phytohaemagglutinin. This inhibitory effect occurs in only 22% of cases
(melatonin-sensitive) but disappears when the cells are stored at 4 degrees
C for 4 days. The effect of melatonin appears not to be mediated by opiates
nor to be correlated with the age, sex, or blood group of donors, but seems
to be influenced by the seasonal time of blood collection."
---
Brackowski R, et al., "Preliminary Study on Modulation of the Biological
Effects of Tumor Necrosis Factor-alpha in Advanced Cancer Patients by the
Pineal Hormone Melatonin" J Biol Regul Homeost Agents 1994; 8: 77
"Lymphocyte mean number observed at the end of TNF infusion was
significantly higher in patients treated with TNF plus MLT than in those
receiving TNF alone."
---
Lissoni P et al., "Immunological Effects of a Single Evening Subcutaneous
Injection of Low-dose Interleukin-2 in Association with the Pineal Hormone
Melatonin in Advanced Cancer Patients." J Biol Regul Homeost Agents
1992; 6: 132
"This study would suggest that a single daily injection of low-dose IL-2 is
able to efficiently activate the lymphocyte proliferation in cancer patients
when it is given in association with the pineal hormone MLT."
Stefano says melatonin reduces TNF and IFN. Brackowski says melatonin
overcomes TNF and increases lymphocytes. Lissoni says that melatonin
activtes lymphocyte proliferation when given with IL-2.
My work suggests melatonin and DHEA act together in a cycle that is
necessary for proper growth, development, and maintenance of all tissues.
This material about melatonin and these cytokines further supports my
theory of AIDS. This all means that, in AIDS, as in aging, the melatonin -
DHEA cycle has shut down.
James Howard
This is my earlier post on how thalidomide works:
"I have posted my ideas regarding DHEA and AIDS here, numerous times.
You can read it in detail at http://www.naples.net/~nfn03605 on the net.
Anyway, my work suggests melatonin and DHEA cycle to produce growth
and development. In AIDS, my work suggests that DHEA first increases,
then becomes chronic, then is lost, due to over-use. Following the loss of
DHEA, the effects of the other adrenal hormone, cortisol, increase and
cause its usual toxic effects. Since DHEA is a "fat burner," its increase may
cause the wasting syndrome; once it is gone, the cortisol simply makes
things worse. Over production of cortisol, in Cushings syndrome, causes
muscle wasting. So, you see, the increase in DHEA, which is used to
positively affect the immune system, causes fat to burn. When DHEA is
lost, cortisol increases and causes muscle wasting. These probably overlap.
You can read my ideas on this in detail here, or at my website.
If you look at my website, you will see my theory of sleep. This gives more
specifics regarding melatonin and DHEA. When thalidomide was first used,
it was used as a sedative in pregnant women. This use cause severe
deformities. If you will look up the structure of melatonin and thalidomide
(do look them up), you will see why thatlidomide can act as a sedative. You
see, thalidomide will attach to the melatonin receptor. Now, melatonin will
inhibit production of DHEA, according to my sleep mechanism. Melatonin
will do this when DHEA is "running out" at the end of the day. Evolution
designed melatonin so that its effects are not absolute; when predators
come around, we need to awaken from sleep relatively easily. Thalidomide,
I suggest, will bind to the receptor and "stick." Pregnancy is a time when a
mother produces a lot of DHEA for herself and her baby. Thalidomide had
to have a stronger effect than melatonin to overcome the arousing effects of
the DHEA of prenant women.
The problem is that DHEA is necessary for growth and development. (If
DHEA is not super-stimulated, as in AIDS, then it leads to growth and
development and fat deposition. This involves the form of DHEA called
DHEAS. When the ratio of DHEAS is higher than DHEA, fat depostion can
occur. In AIDS the DHEAS is low, see my posts or page for further
explanation.) When thalidomide was given to pregnant women, it did not
affect their growth and development; it affected their fetuses.
Thalidomide will block the effects of over-stimulated DHEA, if I am correct.
Perhaps it will inhibit the effects of cortisol. Anyway, I suggest that
thalidomide exerts its "anti-wasting" effects in AIDS by blocking either DHEA
or cortisol. Since I think DHEA is a positive, it promotes lean muscle mass, I
think one should be careful when they use thalidomide. It should be used
only as an "anti-cortisol" agent. Perhaps, supplementing with DHEA may be
better than using thalidomide.
James Howard"
