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Immune System
Signals From Nervous System Influence Immune System, Study
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11-19-2001
In a discovery that demonstrates a clear link between the
mind and body at a molecular level, scientists have shown
that a chemical signal which normally allows nerve cells
to communicate with each other –to alter sleep cycles,
for example -- can also re-direct actions of the immune
system.
The
research in mice confirms mounting evidence from studies
of cultured cells that the nervous system directly influences
the immune system. It has prompted new experiments to determine
if the nerve-generated signal or its receptors in the immune
system might make good drug targets to control asthma or
allergies.
"This
is the first clue of a practical pharmacological approach
to using the nervous system for both improving immune defenses
and damping harmful immune responses at their roots in diseases
as diverse as arthritis and asthma," said Edward Goetzl,
MD, professor of medicine and immunology at the University
of California, San Francisco.
Goetzl
is lead author on a scientific paper on the research in
the November 20 issue of the Proceedings of the National
Academy of Sciences. The work is a collaboration between
UCSF and the University of Edinburgh. Goetzl is also senior
author on a companion paper on the research in FASEB Journal.
(FASEB stands for the Federation of the American Societies
for Experimental Biology.)
The
finding is based on experiments with "knockout"
mice whose immune cells can’t receive the normal neuropeptide
signal known as vasoactive intestinal peptide, or VIP.
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In the nervous system, VIP normally stimulates nerve
cell signaling and survival, and regulates neural biological clocks.
The scientists found that VIP also affects the migration of the immune
system’s T cells and T cell secretion of protein signals for
other immune cells, both of which are central to the body’s
normal defense against infection. Through its action on T cells, VIP
can affect the process in which the immune system turns against the
body, such as in asthma and arthritis.
In the PNAS paper and in the companion paper in the
FASEB Journal, the researchers showed that the strength of the VIP
signal received by the T cells regulates the balance between two types
of immune T cells, Th1 and Th2. Th1 is normally involved with protection
from bacterial invasion and other defenses, but Th1 in excess can
lead to autoimmune disorders. Th2 protects from parasitic infections
and autoimmunity, but in excess can lead to allergies.
The researchers discovered the effect of VIP on the
Th1/Th2 balance by examining the relative production of the Th cells’
protein products, known as cytokines. When the balance is tipped toward
Th1 in knockout mice lacking a critical form of a VIP receptor, allergy
is suppressed and resistance to some types of infections is boosted,
along with other reactions, they found.
The research did not determine if the impact of the
neuropeptide VIP is sufficient to change the course of infections,
inflammation or autoimmune disease in which T cells are involved.
The researchers caution that VIP has such broad effects
on immune function that blocking its action with drugs might risk
triggering one kind of immune malady while it relieves another. However,
the new findings clearly demonstrate the potential of neuroregulation
of T cell functions and suggest the potential value of developing
VIP-like drugs with greater immune selection than VIP itself, Goetzl
added.
Senior author on the PNAS paper is Anthony Harmar,
PhD, professor of neurosciences at University of Edinburgh. Co-authors
are post-doctoral fellows Julia K Voice, PhD, and Glenn Dorsam, PhD,
in the UCSF medicine and immunology departments; and Yvonne Kong,
research assistant in the same departments. Also on the study are
post-doctoral fellows Sanbing Shen, PhD; Katrine M. West, PhD; and
Christine F. Morrison, PhD, all at University of Edinburgh.
The research was funded by the National Institutes
of Health and the Medical Research Council of the United Kingdom.
This
article has been adapted from a news release issued by University
Of California - San Francisco, www.ucsf.edu.
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