• Autoantigen recognition by specific T cells may initiate a tissue-specific immune response in multiple sclerosis (MS), which is a chronic inflammatory demyelinating disorder. During subsequent nonspecific immune amplification, interleukin 1β and tumor necrosis factor α are released by cells of the monocyte/macrophage lineage, with the potential to influence profoundly immune regulation systemically or within the central nervous system. Regulation of monocyte inflammatory gene expression may be relevant to the pathogenesis of MS. We investigated spontaneous secretion of interleukin 1 β, tumor necrosis factor a, and prostaglandin E2 with the use of monocytes that we isolated from patients with active (n=9) and stable (n=9) MS and from age-matched normal controls (n = 9). The patient groups with MS were matched for age, duration of MS, and disease severity. Patients with active disease were within weeks of the onset of a clinical exacerbation. Monocytes were isolated by density gradient centrifugation, followed by adherence to plastic tissue culture flasks, resulting in a highly purified adherent monocyte preparation. Monocytes from patients with active disease spontaneously secreted less tumor necrosis factor α and less prostaglandin E2 compared with that in patients with stable MS, while interleukin 1β levels were below the level of assay sensitivity. Levels of interleukin 1 β and tumor necrosis factor α increased to similar levels in response to lipopolysaccharide (0.1 mg/L), indicating that altered cell viability could not account for the observed differences. In response to lipopolysaccharide, prostaglandin E2 levels increased more significantly in patients with stable than active MS, suggesting differential sensitivity to stimuli of arachidonic acid metabolism. The results documented functional differences between monocytes that were isolated from patients with active compared with stable MS and suggested that peripheral inflammatory monokine secretion parallels MS disease activity.
Rudick RA, Ransohoff RM. Cytokine Secretion by Multiple Sclerosis Monocytes: Relationship to Disease Activity. Arch Neurol. 1992;49(3):265–270. doi:10.1001/archneur.1992.00530270079022
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