Previous studies have suggested conflicting information, including that the diffusible gas induces fever, suppresses fever and plays no role in fever, says Dr. Wieslaw E. Kozak, physiologist and biochemist.

Dr. Kozak's work, published in the June issue of the Journal of Applied Physiology, shows that nitric oxide does indeed have a role in fever regulation, a complicated and surprising one. The article is part of a highlighted topics series on Genetic Models in Applied Physiology featured in the journal's April, May and June issues.

His work to better define the steps of inflammation and resulting fever has implications for finding better ways to treat a host of maladies, from major infections to chronic inflammation that can result in a range of diseases from Alzheimer's to cardiovascular disease to arthritis.

Nitric oxide is produced by at least three enzymes in different tissues throughout the body. Endothelial nitric oxide synthase is found in the endothelial cells of the blood vessels where it plays a big role in blood pressure control. Neuronal nitric oxide synthase is expressed in neuronal cells in the spinal cord, brain, kidney and peripheral nervous system where it works as a cellular messenger. A third enzyme, inducible nitric oxide synthase, is induced by inflammatory agents of the immune system and can be found throughout the body. It may turn out that 'inducible' is a misnomer, because some believe this enzyme always is expressed at some level but that it's over-expressed in inflammation, Dr. Kozak says.

Knockout mice missing one of each of these three enzymes already were available for study, so Dr. Kozak induced fever in the genetically engineered mice, expecting to see a similar course in all three because although the enzymes are different, their p
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Contact: Toni Baker
tbaker@mail.mcg.edu
706-721-4421
Medical College of Georgia
30-May-2003