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Lymphomononuclear cells from multiple sclerosis patients spontaneously produce high levels of oncostatin M, tumor necrosis factors and ß, and interferon

Department of Clinical Medicine, Allergy and Immunology University of Rome `La Sapienza’, Rome 00185, Italy, ensolifior{at}uniroma1.it

V Fiorelli

Department of Clinical Medicine, Allergy and Immunology University of Rome `La Sapienza’, Rome 00185, Italy

A Lugaresi

Department of Oncology and Neuroscience, University `Gabriele d’Annunzio’, Chieti I-66013, Italy

D Farina

Department of Oncology and Neuroscience, University `Gabriele d’Annunzio’, Chieti I-66013, Italy

M DeCristofaro

Department of Clinical Medicine, Allergy and Immunology University of Rome `La Sapienza’, Rome 00185, Italy

B Collacchi

Department of Clinical Medicine, Allergy and Immunology University of Rome `La Sapienza’, Rome 00185, Italy

D Santini Muratori

Department of Clinical Medicine, Allergy and Immunology University of Rome `La Sapienza’, Rome 00185, Italy

E Scala

Department of Clinical Medicine, Allergy and Immunology University of Rome `La Sapienza’, Rome 00185, Italy

M Di Gioacchino

Department of Oncology and Neuroscience, University `Gabriele d’Annunzio’, Chieti I-66013, Italy

R Paganelli

Department of Clinical Medicine, Allergy and Immunology University of Rome `La Sapienza’, Rome 00185, Italy

F Aiuti

Department of Clinical Medicine, Allergy and Immunology University of Rome `La Sapienza’, Rome 00185, Italy

Proinflammatory cytokines are deemed to play a pivotal role in the pathogenesis of multiple sclerosis (MS). They provide signals for T-cell activation and inflammatory cell recruitment in the brain and might directly alter neuroglial and neuronal cell survival and function. We found that peripheral blood mononuclear cells (PBMCs) from MS patients spontaneously produce high levels of TNF, TNFß, IFN, and oncostatin M (oncM), a proinflammatory cytokine acting on cells of neural, vascular, hematopoietic, and lymphoid origin. Spontaneous production of these cytokines was significantly higher (p<0.01) in PBMC short-term culture supernatants from MS patients than in blood donors (HC). On average, lectin-induced production of these cytokines by PBMC was higher in MS patients than in HC, significantly so only for TNF (p=0.013). Determination of TNF, TNFß, IFN, and oncM in corresponding sera showed that, on average, oncM levels were higher in MS patients than in HC, though the results were not statistically significant, whereas levels of TNF, TNFß, and IFN were below the assay threshold in most patients. The finding that MS PBMCs are primed in vivo to produce and release high levels of proinflammatory cytokines suggests the presence of a basal activation of the immune system which, in turn, may play a role in the complex circuitry of molecular and cellular interactions responsible for neurologic damage in MS.

Key Words: cell cultures • cytokines • demyelinating diseases • ELISA • interferon • mononuclear cells • multiple sclerosis • oncostatin M

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