Monday, June 29, 2009

Treatments may be ready for Gulf War Illness Treatment Trials

Written by Anthony Hardie, 91outcomes

(Boston, Mass. - June 29, 2009) Treatments for Gulf War Illness (GWI) may already be available and ready for testing in treatment trials, said Dr. Keith Kelley during a presentation today in Boston before the federal Research Advisory Committee on Gulf War Weterans' Illnesses.

Kelley is Professor of Immunophysiology in the Integrative Immunology and Behavior Program and Neuroscience Program and the Department of Animal Sciences at the University of Illinois at Urbana-Champaign.

During his presentation, entitled, The role of neuroinflammation in chronic illness, Dr. Kelley explained what it actually means "to be sick" from a scientific perspective, which includes increased temperature, decreased social and physical activity, and other effects, and noted that many of these correlate with key aspects of the current definition of Gulf War Illness, including affected learning and memory, mood changes, and unrelenting fatigue.

While there is currently a lack of treatments for Gulf War Illness, Dr. Kelley said he believes that the current neuroinflammation hypothesis of Gulf War Illness is worth testing because FDA-approved drugs to reduce neuroinflammation from pre-clinical animal studies are available. According to Dr. Kelley, neuroinflammation reduces appetite, motivation, increases exhaustive fatigue and sensitivity to pain, causes deficits in learning and memory, and induces depressive-like behaviors.

Dr. Kelley suggested that potential treatments that would be valuable to study with regards to the neuroinflammatory model of Gulf War Illness may include:
According to Dr. Kelley's biography, his research interests include proinflammatory cytokines and hormones in the brain and in cancer and muscle cells:

"For the past 30 years, our laboratory has been involved in defining reciprocal systems of communication between the immune and central nervous systems. We currently are interested in defining receptor signaling pathways that occur following activation of receptors for both proinflammatory cytokines and growth factors in the brain and the periphery and the role of inflammation in mental health disorders. For the former, we have discovered the existence of intracellular crosstalk between receptors for proinflammatory cytokines (TNFalpha, IL-1beta) and hormones (IGF-I) in a variety of cells. This interaction reduces the ability of growth factor receptors to function in the presence of very low concentrations of proinflammatory cytokines.

"The result is that the biological response of cells to a growth factor, whether it is the proliferation of cancer cells or the differentiation of muscle progenitor cells, is reduced in the presence of proinflammatory cytokines. Collectively, these data show that the biological properties of a classical hormonal growth factor receptor are directly regulated by proinflammatory cytokines from the immune system. For the second major emphasis in our laboratory, major research projects are aimed at determining the actions of proinflammatory cytokine receptors that are involved in sickness behavior, depressive-like behavior and memory. Brain inflammation causes symptoms of sickness that are usually associated with microbial infections, which is likely to make an important contribution to the comorbid behavioral and psychological disturbances that occur in the elderly.

"We have shown that IL-1beta and TNFalpha serve as communication molecules between the immune and central nervous systems. In contrast, anti-inflammatory cytokines in the brain, such as IL-10 and IGF-I, reduce behavioral symptoms of sickness following infection. We now are exploring the influence of aging on development of depressive-like behaviors in mice because one in five individuals over the age of 65 suffer from depressive disorders. This is more than twice the prevalence found in the general population.

"A likely mechanism for the increased prevalence of depressive disorders during aging is a reduction in the synthesis of serotonin, a key neurotransmitter in the regulation of mood, caused by proinflammatory cytokines acting in the brain. This action is mediated by immune-induced activation of the tryptophan-degrading enzyme, indoleamine 2,3 dioxygenase (IDO). This process decreases the bioavailability of tryptophan for the synthesis of serotonin.

"We are measuring IDO enzymatic activity, tryptophan and its metabolism (serotonin, 5-HIAA, kynurenine) in discrete brain regions of aged mice given either LPS or BCG. The major health impact of our research is directed at cognitive function, affect and muscle wasting in AIDS, cancer and aging."

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