WESTPORT, Mar 22 (Reuters Health) - Short- and long-term treatment with type I interferons have opposing effects in a murine model of multiple sclerosis, according to a report in the March 1st issue of the Journal of Neuroscience Research.
Dr. Moses Rodriguez, of the Mayo Clinic and Foundation in Rochester, Minnesota, and colleagues compared the short-term (5 weeks) and long-term (16 weeks) effectiveness of type I interferon (IFN-alpha/beta) treatment of CNS demyelination in mice infected with Theiler's murine encephalomyelitis virus.
In the short-term experiments, spinal cord white matter demyelination did not differ between treatment and control mice. "Mice treated with IFN-alpha/beta for 5 weeks...demonstrated threefold increase in oligodendrocyte remyelination when compared to age-matched infected mice treated with sterile phosphate-buffered saline," the authors report.
In contrast, in the long-term experiments, mean white matter demyelination was 15.6% in saline-treated mice and 28.7% in IFN-treated mice. Although the area of remyelination was also increased, the investigators note, "because of the increased extent of demyelination, the percent of demyelinated area exhibiting remyelination was not increased."
Neither short- nor long-term treatment with IFN-alpha/beta affected the number of virus RNA-positive cells in the spinal cord white matter, the researchers observe. They infer that both enhanced remyelination with short-term treatment and exaggerated demyelination with long-term treatment were independent of the level of virus present.
Short-term treatment caused no significant adverse effects, but long-term treatment was associated with a transient anorexia resulting in temporary deterioration in the animals' condition. According to the results, these effects resolved by the tenth week of treatment.
"The paradoxical results that long-term IFN-alpha/beta treatment aggravates demyelination whereas short-term treatment potentiates remyelination suggests a delicate balance between harmful and beneficial effects of IFN-alpha/beta," the authors conclude. "If a similar balance is present in MS plaques, then these results may have important implications on the long-term use of type I IFN in human MS patients."
J Neurosci Res 2000;59:661-670.