T cell lymphokine-induced secretion of cytokines by monocytes from patients with multiple sclerosis.
To investigate the function of peripheral blood monocytes in multiple sclerosis (MS), we measured the production of the cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6), and the procoagulant, tissue factor (TF) in 17 patients with chronic progressive MS and 15 normal controls. Monocyte activity was tested under unstimulated, minimal endotoxin conditions and after culture with various stimuli, including Escherichia coli lipopolysaccharide (LPS), crude supernatant from anti-CD3-activated T cells, recombinant interleukin-2 (rIL-2), and recombinant interferon-gamma (rIFN-gamma). A higher number of MS patients than controls had circulating monocytes which spontaneously secreted IL-6 or contained detectable cell-associated IL-1 beta. Monocyte responses to LPS were comparable between the two groups; LPS caused production and secretion of all cytokines and TF in every MS patient and control. In contrast, crude T cell supernatants, rIL-2, and rIFN-gamma induced IL-1 beta release in a higher number of MS monocytes than that in controls, whereas the production and secretion of the other cytokines and TF activity were similar between the groups. We conclude that some MS patients have "primed" circulating monocytes, as shown by excessive spontaneous IL-6 release and intracellular IL-1 beta synthesis. Unstimulated MS monocytes, however, are not different from controls with respect to spontaneous secretion of small amounts of IL-1 beta and TNF alpha and expression of cell surface TF. Excessive IL-1 beta secretion by MS monocytes after stimulation with T-cell-derived lymphokines suggests dysregulation of T cell-monocyte interactions which may be most relevant in the central nervous system plaques where activated T cells are found.
Maimone
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Department of Neurology, University of Chicago, Illinois 60637.
Reder
A T
AT
Gregory
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S
D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000032:analysis*; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000032:analysis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D013925:Thromboplastin / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D013925:Thromboplastin