Interferon effects on interleukin-10 secretion. Mononuclear cell response to interleukin-10 is normal in multiple sclerosis patients.
The mechanism of action of recombinant interferon beta 1b (rIFN beta 1b/IFN beta-1b), the approved therapy for multiple sclerosis (MS), is still unclear. Here we present evidence that part of the therapeutic effects of rIFN beta 1b in MS might result from the induction of the secretion of interleukin (IL)-10, a cytokine previously designated cytokine synthesis inhibitory factor (CSIF). We observed that rIFN beta 1b stimulated significant IL-10 secretion by monocytes from MS patients after brief incubation (18 h), whereas rIFN gamma, an inducer of MS exacerbations, was unable to stimulate IL-10 production in similar conditions. To determine the role of IL-10 as CSIF in the disease, we have also investigated its effects on TNF alpha and IL-6 secretion by peripheral blood mononuclear cells from MS patients. Recombinant human IL-10 significantly inhibited tumor necrosis factor alpha and IL-6 secretion induced by rIFN gamma, lipopolysaccharide (LPS), and rIFN gamma + LPS in MS patients and in control subjects. The induction of IL-10 secretion by rIFN beta 1b and the IL-10 inhibitory activity on pro-inflammatory cytokine secretion induced by rIFN gamma in MS make this cytokine a potential candidate to treat the disease.
Porrini
A M
AM
Institute of Clinical Neurology and Behavioral Sciences, University of Chieti, Italy.
Gambi
D
D
Reder
A T
AT
D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016899:Interferon-beta; D007371:Interferon-gamma