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Endotoxin: is it an environmental factor in the cause of Parkinson’s disease?
  1. I Niehaus1,
  2. J H Lange2
  1. 1Lübeck, Germany
  2. 2Envirosafe Training and Consultants, Inc., PO Box 114022, Pittsburgh, PA 15239, USA; john.pam.lange{at}worldnet.att.net

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    Occurrence of Parkinson’s disease (PD) has been reported to be associated with environmental factors, notably those associated with employment in the agricultural industry.1 Some have suggested that the agent associated with agriculture is pesticide exposure, although no specific class of pesticide has been identified.2

    We suggest that besides pesticides, endotoxin (lipopolysaccaride, LPS) may also be an environmental factor. Endotoxin is a common airborne environmental and occupational contaminate in agricultural3 and other industries.4,5

    Endotoxins are part of the outer cell wall of Gram negative bacteria.6 This agent can elicit a multitude of pathophysiological effects, including inflammation, macrophage activation, fever, and septic shock.7,8 The blood-brain barrier can become leaky as a result of sepsis,9 allowing LPS to enter the cerebrospinal fluid.

    Experimentally, endotoxin has been shown to cause inflammation in the dopaminergic neurones of the substantia nigra, resulting in pathogenesis of PD.10,11 LPS stimulate astrocytes and microglia in the CNS to secrete cytokines such as TNF-α, IL-6, and IFN-γ.10 Microglial activation preceded the apparent neuronal degeneration.11

    One case study12 reported that a 22 year old laboratory worker developed Parkinson’s syndrome, with bradykinesia, rigidity, tremor, and cogwheel phenomenon, three weeks after accidental exposure to 10 μg Salmonella minnesota LPS through an open wound. The LPS caused a chronic inflammation in the nervous system (6600 pg LPS/ml cerebrospinal fluid), which was also characterised by neuralgic pain, polyneuropathy, and encephalopathy, with difficulties in short term memory, learning, and spatial orientation. Damage to the substantia nigra and cerebral cortex was shown by positron emission tomography.

    In another case study13 a laboratory worker would have died without medical help because of severe sepsis after a single injection of 1 mg of Salmonella minnesota LPS. This shows the potency of endotoxin in physiological responses.

    The case event of PD is supported by animal experimentation.14 Several animal studies10,11,14 have shown that LPS causes damage to the substantia nigra, resulting in PD. These animal investigations support the hypothesis that LPS may be one of the environmental factors that trigger PD. A recent study15 suggests that LPS may be an important contributor to exacerbation of inflammatory disease resulting from particulate matter associated with air pollution. This shows the diverse influences of LPS on physiological systems.

    It is suggested that LPS is one of the causes for postencephalitic parkinsonism after encephalitis from Gram negative bacteria. These findings warrant further investigation of this potential environmental factor.

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