Lymphomononuclear cells from multiple sclerosis patients spontaneously produce high levels of oncostatin M, tumor necrosis factors alpha and beta, and interferon gamma.
Proinflammatory cytokines are deemed to play a pivotal role in the pathogenesis of multiple sderosis (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 patents spontaneously produce high levels of TNFalpha, TNFbeta, IFNgamma, and oncostatin M (oncM), a proinflammatory cytokine actng 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 patents than in HC significantly so only for TNFalpha (p = 0.013). Determination of TNFalpha, TNFbeta IFNgamma, 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 TNFalpha, TNFbeta and IFNgamma 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.
Ensoli
F
F
Department of Clinical Medicine, Allergy and Immunology University of Rome La Sapienza, Italy. ensolifior@uniroma1.it
Fiorelli
V
V
Lugaresi
A
A
Farina
D
D
De Cristofaro
M
M
Collacchi
B
B
Muratori
D Santini
DS
Scala
E
E
Di Gioacchino
M
M
Paganelli
R
R
Aiuti
F
F
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis* / Q000097:blood; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000032:analysis / Q000097:blood; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology*; D053683:Oncostatin M; D010455:Peptides / Q000032:analysis* / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D016207:Cytokines; D008233:Lymphotoxin-alpha; C508351:OSM protein, human; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D007371:Interferon-gamma