INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 12: 485-492, 2003

Cyclic exercise induces anti-inflammatory signal molecule
increases in the plasma of Parkinson's patients
PATRICK CADET
1
, WEI ZHU
1
, KIRK MANTIONE
1
, MARILYN RYMER
2
, IRVING DARDI

It has been known for many years that immune
system alterations occur with Parkinson's disease (PD).
Changes in lymphocyte populations in cerebrospinal fluid
and blood, immunoglobulin synthesis, and cytokine and acute
phase protein production have been observed in patients with
PD. Hence, there is evidence for inflammation. In this report
we demonstrate that cyclic exercise over months results in a
significant increase in the rise of plasma anti-inflammatory
signal molecules, such as interleukin-10 and adrenocortico-
tropin. Additionally, endogenous plasma morphine levels
increase with the duration of the cyclic exercise protocol.
Morphine is identified and quantified by high performance
liquid chromatography coupled to electrochemical detection
and nano electro-spray ionization double quadrupole
orthogonal acceleration time of flight mass spectrometry.
Proinflammatory cytokine, i.e., interleukin-1, interleukin-6,
plasma levels did not increase. These results matched with
those reported previously, demonstrating enhanced motor
skills and mood elevation with this cyclic exercise protocol,
suggest that this protocol induces the formation of anti-
inflammatory signal molecules, which appear to be associated
with alleviation of some of the clinical characteristics of PD.
Introduction
Idiopathic Parkinson's disease is a degenerative disorder of
the central nervous system. Several pathogenic mechanisms
have been proposed that lead to degeneration of dopamin-
ergic neurons. These mechanisms encompass variables such
as metabolic or toxic factors, oxidative stress and mito-
chondrial dysfunction (1). The primary anatomical features
central to PD patients include: a diminished number of
myelinized dopaminergic cells in the substantia nigra (SN)
and in related brain stem nuclei, a decrease in the dopamine
content in nigrostriatal and mesolimbic pathways, the
presence of Lewy bodies, and the deposition of neuromelanin
(2,3). The perturbation of several neurotransmitters and
neuropeptides has been reported in PD, indicating a more
complicated and widespread pathology. The role of immune
and vascular mechanisms in neurodegenerative diseases such
as PD is, similarly, an important area of investigation (1,4).
Death or injury to neurons in PD leads to the presence of many
pro-inflammatory cytokine molecules, as well (1). This process
resembles classic inflammation, but with minimal or no
participation of macrophages and lymphocytes from blood (1).
In the present report, we determine the plasma level of
pro-and anti-inflammatory cytokines as well as signal mole-
cules most often associated with stress, i.e., adrenocortico-
tropin (ACTH) at baseline (group 1). We also measure these
levels subsequent to the introduction of a 12 week cyclic
exercise regime at week 4 (group 2), week 8 (group 3) and
week 12 (group 4). We demonstrate that anti-inflammatory
signal molecules significantly appear in the plasma months
after initiating and sustaining this cyclic exercise protocol.
These results are correlated with a previous study, which found
that cyclic exercise in Parkinson's patients produced
improvement in motor function and attitude


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