More on DHEA, Testosterone and Infections

jmhoward at sprynet.com jmhoward at sprynet.com
Thu Dec 31 10:29:57 EST 1998


More on DHEA, Testosterone and Infections

James Michael Howard
Fayetteville, Arkansas, U.S.A.

I have posted here, and elsewhere, regarding my hypothesis that proper
amounts of the hormone, DHEA, are necessary for immune defense against
viruses, specifically the HIV.	One may read this in my article concerning
AIDS at my webpage, http://www.naples.net/~nfn03605/, or at my recent post,
possibly here, entitled: “Why the HIV is so Prevalent in Africa.”  It is also
my hypothesis that sufficient DHEA is necessary for immune defense against
bacteria.  (This is within my article on AIDS at the webpage.)	I just
recently found the following quotation (at the end of this post) which
directly supports my hypothesis regarding DHEA and bacteria and also supports
my ideas concerning the influence of testosterone in infections.  That is, my
post regarding the HIV in Africa deals with the inhibitory effect of
testosterone on DHEA enhancement of the immune system. The quotation, which I
just found and which caused me to write this post, deals with the inhibitory
effects of testosterone on the immune system, and it includes the conclusion:
“The finding that DHEA markedly improves the depressed immune functions and
survival of animals subjected to subsequent sepsis suggests that short-term
treatment with DHEA after trauma-hemorrhage is a safe and novel approach for
preventing immunodepression and for decreasing the mortality rate due to
subsequent sepsis.”

February 11, 1996, page 3F, my “letter to the editor” of “The Morning News of
Northwest Arkansas” included the following which includes my explanation of
the connection of DHEA and testosterone in infections.	(I omitted the
introductory material and the conclusion.)

“The Jan. 17 article reported that a lot of the increase in bacterial
infections may be due to ‘antibiotic resistance.’  Healthy people are exposed
to infectious bacteria constantly, including antibiotic resistant types, yet
they stay healthy.  Antibiotics are used when our bodies cannot fight
bacteria alone, therefore, antibiotic resistant bacteria are a real problem. 
However, people who cannot sufficiently fight bacteria cannot fight the
bacteria for a reason; antibiotics are not a cure, they are a help.  The
article also reported that: ‘Mortality from septicemia, a rapid form of
bacterial blood poisoning, increased 83 percent, and deaths from respiratory
tract infections rose 20 percent.  The increase in respiratory deaths stems
mostly from an aging population, but Pinner couldn’t explain the septicemia
increase.’  A younger population is dying from septicemia.”

The article of Jan 24 stated that ‘Anyone can get TB, but some people are at
higher risk such as: people with HIV, foreign-born people from countries
where a lot of people have TB, nursing home residents, prisoners and
alcoholics and intravenous drug users.’  According to my work, people of low
DHEA and high testosterone/low DHEA are more prone to infections.  People
with HIV are proven to be low in DHEA and men are more infected by the HIV
than other groups. Nursing home residents are proven to be low in DHEA, and
the ones that require the most care have even lower DHEA (J. Am. Geriatric
Society 1990; 38: 421). My work suggests people of high testosterone are more
impulsive; they commit more crimes.  This is why more men are in prison than
women and why more black men are in prison than white men (black men produce
significantly more testosterone, J. Nat. Cancer Institute 1986; 76: 421). 
This also explains the ‘unexpected finding that under the same social
conditions, blacks are apparently infected more by Mycobacterium tuberculosis
than whites,’ (The New England Journal of Medicine 1990; 433: 422).  Aging
people and the very young are also more vulnerable to infections.  These are
all groups of low DHEA, or low DHEA in addition to high testosterone.”

The first quotation below is the quotation to which I referred above.  It is
also my hypothesis that the hormone, melatonin, interacts with DHEA in a
“melatonin-DHEA cycle.”  I think these two hormones interact in the
production of the other.  The second quotation below reports the very similar
finding that: “This is the first study to show that melatonin, which is
reported to be free of adverse side effects, can be considered a safe and
effective therapeutic agent for restoring the depressed immunological
function after soft- tissue trauma and hemorrhagic shock.”

Arch Surg 1998 Dec;133(12):1281-8 “Dehydroepiandrosterone: an inexpensive
steroid hormone that decreases the mortality due to sepsis following
trauma-induced hemorrahage” Angele MK, Catania RA, Ayala A, Cioffi WG, Bland
KI, Chaudry IH Center for Surgical Research, Department of Surgery, Brown
University School of Medicine, Rhode Island Hospital, Providence 02903, USA.

“BACKGROUND: Recent studies suggest that male sex steroids play a role in
producing immunodepression following trauma-hemorrhage. This notion is
supported by studies showing that castration of male mice before trauma-
hemorrhage or the administration of the androgen receptor blocker flutamide
following trauma-hemorrhage in noncastrated animals prevents immunodepression
and improves the survival rate of animals subjected to subsequent sepsis.
However, it remains unknown whether the most abundant steroid hormone,
dehydroepiandrosterone (DHEA), protects or depresses immune functions
following trauma-hemorrhage. In this regard, DHEA has been reported to have
estrogenic and androgenic properties, depending on the hormonal milieu.
OBJECTIVE: To determine whether administration of DHEA after
trauma-hemorrhage has any salutary or deleterious effects on immune
responses, and whether it improves the survival of animals subjected to
subsequent sepsis. DESIGN: Male C3H/HeN mice underwent laparotomy (ie,
trauma-induced) and hemorrhagic shock (blood pressure, 35+/-5 mm Hg for 90
minutes) followed by fluid resuscitation, or sham operation. The animals then
received 100 mg of DHEA (4 mg/kg) or propylene glycol (hereafter referred to
as vehicle). At 24 hours after trauma-hemorrhage and resuscitation, the
animals were killed and blood, spleens, and peritoneal macrophages were
harvested. Splenocyte proliferation and interleukin (IL) 2 release and
splenic and peritoneal macrophage IL-1 and IL-6 release were determined. In a
separate set of experiments, sepsis was induced by cecal ligation and
puncture at 48 hours after trauma-hemorrhage and resuscitation. For those
studies, the animals received vehicle, a single 100-microg dose of DHEA, or
100 microg/d DHEA for 3 days following hemorrhage and resuscitation. Survival
was monitored for 10 days after the induction of sepsis. RESULTS:
Administration of DHEA restored the depressed splenocyte and macrophage
functions at 24 hours after trauma-hemorrhage. Moreover, daily administration
of DHEA for 3 days significantly increased the survival of animals subjected
to subsequent sepsis (P=.01). CONCLUSION: The finding that DHEA markedly
improves the depressed immune functions and survival of animals subjected to
subsequent sepsis suggests that short-term treatment with DHEA after
trauma-hemorrhage is a safe and novel approach for preventing
immunodepression and for decreasing the mortality rate due to subsequent
sepsis.”

J Surg Res 1996 Jun;63(1):256-62
“Melatonin administration attenuates depressed immune functions trauma-
hemorrhage”
Wichmann MW, Zellweger R, DeMaso, Ayala A, Chaudry IH
Shock and Trauma Research Laboratories, Department of Surgery, Michigan State
University, East Lansing 48824-1315.

“The pineal hormone melatonin has been used in clinical trials in patients
suffering from AIDS and also as an adjuvant for cancer therapy. Although
melatonin has been reported to have beneficial effects in some animal models
of immune dysfunction, it remains unknown whether this hormone has any
salutary effects on immunity following soft-tissue trauma and/or major blood
loss. To study this, soft-tissue trauma (2.5-cm midline laparotomy) and
hemorrhagic shock (arterial BP 35 +/- 5 mm Hg) were induced in C3H/HeN mice.
The mice were resuscitated after 90 min of hypotension with the shed blood
and lactated Ringer's solution. Treatment with saline, vehicle, or melatonin
(10 mg/kg BW) subcutaneously was administered in the evening of the day of
surgery and again on the following evening. All animals were sacrificed at 48
hr following trauma- hemorrhage and resuscitation to obtain plasma,
splenocytes, as well as splenic and peritoneal macrophages (Mphi). The
results indicate that melatonin administration after trauma-hemorrhage
significantly improved the depressed immune functions, as evidenced by the
restoration of Mphi IL-1 and IL-6 release, as well as significantly improved
splenocyte IL-2 and IL-3 release and splenocyte proliferative capacity. No
differences in circulating corticosterone levels between vehicle- and
melatonin-treated animals were observed. This is the first study to show that
melatonin, which is reported to be free of adverse side effects, can be
considered a safe and effective therapeutic agent for restoring the depressed
immunological function after soft-tissue trauma and hemorrhagic shock.”

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