10/28/98 COLUMBUS, Ohio -- Researchers here have proposed a new theory for the cause of chronic fatigue syndrome (CFS) -- one that blames the illness both on a low-level viral infection and on the body’s own immune response to that virus.

If true, it would offer an explanation for why virologists so far haven’t found evidence of a common virus when looking at a population of CFS patients. The hypothesis was included in a paper published in the current issue of the American Journal of Medicine.

The new theory, proposed by Ronald Glaser, professor of medical microbiology and immunology, and Janice Kiecolt-Glaser, professor of psychology and psychiatry at Ohio State University, is the latest work in more than two decades of their research on the effects of stress on the human immune system.

"Our data suggests that stress may be causing the expression of certain viral proteins and that these proteins may be modulating the body’s immune response, turning it on or off," Glaser said.

CFS was first characterized by researchers in the mid-1980s who described it as a combination of symptoms including low-grade fevers, body aches, malaise, and depression among other signs. The condition seems more prevalent among young adult women. Those diagnosed with CFS often experience stress and depression.

Symptoms routinely linger for six months or more and may continue for years. The federal Centers for Disease Control and Prevention estimate that CFS may affect anywhere from four to 10 of every 100,000 people in the United States.

Other researchers have reported higher-than-normal titers of antibodies to various latent viruses -- Epstein-Barr virus, cytomegalovirus, human herpes virus 6, for example -- in the blood of patients diagnosed as having CFS. But no one viral infection was present in all patients -- evidence that would be needed to prove a viral cause of the illness.

The Ohio State researchers’ new theory poses several mechanisms that might be linked to CFS.

Once a person is infected, these viruses can remain latent in the body for long periods of time. Glaser proposes that the viruses could be partially reactivated, that is, viral proteins could be produced at levels high enough to cause a low-grade infection but too low to be seen using current laboratory assays.

Glaser and Kiecolt-Glaser suggest that CFS patients may experience an ongoing, low-grade viral infection -- more like a smoldering fire rather than a three-alarm blaze -- which could stimulate parts of the immune response without raising antibody titers to typically high levels.

That low-grade infection would be enough to increase production of various cytokines -- chemical mediators for the immune system -- and begin the immune response.

"A lot of the symptoms that you find in chronic fatigue syndrome are the same ones induced by cytokines during our normal immune response," Glaser said.

He admits that studies of patients have yet to show a pattern of abnormal cytokine behavior that would substantiate their theory but he has an explanation for that.

"We haven’t discovered all the cytokines involved in immunity. We may not have found the right one, yet," he said, adding that new cytokines are steadily being identified.

Stress and depression may be playing a related role as well, Kiecolt-Glaser said. Earlier research has repeatedly shown that increased stress and depression can reactivate latent viruses, decrease the body’s immune response, and stimulate the production of certain cytokines linked to some CFS-like symptoms.

"Part of this is a chicken-and-egg problem," Kiecolt-Glaser said. "People diagnosed with CFS often are depressed since they’re unable to carry out normal, daily activities. What we don’t know is whether the depression followed the diagnosis of CFS or if CFS contributed to it.

"We do know, however, that this kind of depression can weaken our immune response."

Glaser said researchers need to reconsider past work on CFS.

"We need to look for immune system changes that are much more subtle and specific than those we’ve been using as benchmarks," he said.

Contact: Ronald Glaser, (614) 292-5526; Glaser.1@osu.edu; Janice Kiecolt-Glaser, (614) 293-5120, Kiecolt-Glaser.1@osu.edu

Written by Earle Holland, (614) 292-8384; Holland.8@osu.edu