Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: Do cytokines trigger off exacerbations?

Abstract

We have carried out a longitudinal study of interferon (IFN) and tumor necrosis factor (TNF) using a whole-blood mitogen stimulation assay in 20 multiple sclerosis (MS) patients and in a healthy control group. We set up individual profiles and the results were quite constant for each individual, both in healthy donors and in the patients in remission. Before exacerbations, however, we found an increase of IFN-gamma and TNF production preceding clinical symptoms by a maximum of 2 weeks. In benign cases, the increase disappeared rapidly, even before the appearance of symptoms, whereas we found sequelae whenever the increase persisted during weeks. In chronic progressive patients, we frequently found intervening increases. It may be that IFN-gamma and TNF trigger off exacerbations at a very early stage and that these cytokines may also play a role in maintaining disease in chronic progressive and invalidating forms.

Nutritional factors and aging in demyelinating diseases

“…MS patients tend to have higher levels of TNFa, both in cerebrospinal fluid and in serum, than control patients. In turn, these values correlate with disease severity (Beck et al 1988;Maimone et al 1991). Interleukin (IL)-1b is another pro-inflammatory cytokine related to the physiopathology of demyelinating diseases such as MS and, similarly to TNFa, is associated with the worsening of CNS pathology (de Jong et al 2002).…”

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis

“…18 IFNg also induces dendritic retraction and inhibits synapse formation. 19 IFNg expression increases in the 2 weeks preceding attacks of MS. 20,21 Low levels of IFNg expression by lymphocytes at the initiation of treatment with IFNb predict a favorable response to treatment. 22 Treatment with exogenous IFNg is deleterious to patients with MS. 23 However, as is the case in EAE, whether endogenous IFNg expression represents a deleterious or a disease limiting effect in MS is unknown.…”

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

“…In this sense, high concentrations of sICAM-1 and VCAM-1 in the peripheral blood during active disease would reflect BBB damage and may further serve as an adhesion ligand during extravasation of activated leukocytes into the brain tissue 24,27 . Indeed the extent of ICAM-1 activation may vary within different regions of the inflamed brain tissue which ultimately may account for the varying degrees of neurological deficit 2,4,28,29 .…”

“…A rise in TNFα production by blood mononuclear cells apparently precedes clinical exacerbations and is associated with active inflammatory lesions 28 . Indeed, the severity of the relapse, measured by the EDSS score, highly correlate to the TNF production 29,30 .…”