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FOR IMMEDIATE RELEASE
Contact:
Donna Krupa
703.527.7357 (direct
dial)
703.967.2751 (cell) or
djkrupa1@aol.com
HORMONAL CHANGES DURING PHYSIOLOGICAL DEVELOPMENT CAN
ALTER IMMUNE RESPONSE TO VIRUSES AND INFECTIONS
Researchers Release Results of New Study, Sex
Differences in Hantavirus Infection: Interactions Among Hormones, Genes and
Immunity
PITTSBURGH, Pa. -- It is generally recognized
among immunologists that males of all species have lower immunity than
females. Men are more susceptible to a variety of infections, such as
dysentery, gonorrhea, and malaria; and to certain cancers. Females are at
greater risk of illnesses caused by an overactive immune system, such as
systemic lupus erythematosus, diabetes ulcerative colitis, and arthritis.
Why men and women respond differently to infections
caused by viruses or other parasites remains a mystery. How the immune
system adopts certain strategies towards particular illnesses has not been
determined. Examining gender characteristics, hormones and genes, and how
they interact with immunology could provide answers to these questions.
This was the goal of a team of Johns Hopkins researchers as they set out to
determine how differences in sex are expressed in rats' response to
hantaviruses (sex differences in hantaviruses represent an ecologically and
clinically relevant model for studies of sex-based differences in
infection).
Researchers Sabra L. Klein, Ph.D., A.L. Scott, and G.E.
Glass, Ph.D., all from the Department of Molecular Microbiology and
Immunology, The Johns Hopkins University Bloomberg School of Public Health,
Baltimore, Md., have conducted a study on “Sex Differences in Hantavirus
Infection: Interactions Among Hormones, Genes, and Immunity.” Their findings
are to be presented at the conference, Genomes and Hormones: An
Integrative Approach to Gender Differences in Physiology, being
sponsored by the American Physiological Society (APS) October 17-20, 2001,
at the Westin Convention Center, Pittsburgh, Pa.
Methodology and Results
These researchers first set out to determine if
manipulating sex steroids in adult rodents would impact the response to
inoculation with the Seoul virus (a Hantavirus that naturally occurs in
Norway rats). The researchers found that in the male rats, the production
of antibodies increased, enhanced Th1 responses (inflammatory responses)
against infection occurred, and shed or released the virus into the
environment for a longer time period than comparable females in the study.
Accordingly, hormone manipulation in female and male adult rodents had no
effect on their normal response to virus infection.
In all animals (including humans), sex steroid hormones affect
gender-specific development at two distinct times. During perinatal (i.e.,
during prenatal and early postnatal) development, sex steroids cause
permanent, hard-wired differences in the organization of central and
peripheral physiology (i.e., organizational effects). After puberty,
exposure to sex steroids serves to transiently activate pre-existing
hormonal circuits (i.e., activational effects). In mammals, masculine
development is induced by early exposure to testosterone, whereas feminine
development occurs in the absence of testosterone. Because manipulation of
hormones in adult animals had no effect on responses to viral infection,
these researchers hypothesized that hormones may hard-wire gender-specific
immune responses earlier during development.
Therefore, the next step in the study was to determine
if neonatal manipulation of sex hormones organized adult responses to the
hantavirus administered to rats. After two to four days of age, male rats
were castrated and females were injected with testosterone. All animals
were inoculated with the Seoul virus as adults; antibody responses and viral
prevalence were assessed in both sexes.
Castrated males displayed female-type responses, i.e.
lower concentrations of anti-virus responses with less virus shed than in
the control male population. On the other hand, injecting testosterone into
female neonatal mice had no impact on that group's response to infection.
Conclusions
Altering the immune response to infection occurs at a
neonatal stage, as evidenced by the lowering levels of testosterone in male
mice. However, manipulating testosterone levels in female mice had no
impact on the immune system. These results suggest that the preponderance
of gender-related immunological diseases must be related to mechanisms other
than sex steroids alone, possibly genetic differences between the sexes.
-end-
The
American Physiological Society (APS) was founded in 1887 to foster basic and
applied science, much of it relating to human health. The Bethesda,
MD-based Society has more than 10,000 members and publishes 3,800 articles
in its 14 peer-reviewed journals every year.
***
Editor’s Note: To receive a copy of the abstracts, to interview speakers or
for more information, contact Donna Krupa at 703.527.7357(direct dial),
703.967.2751 (cell) or djkrupa1@aol.com.
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