Correlation between disease severity and in vitro cytokine production mediated by MSRV (multiple sclerosis associated retroviral element) envelope protein in patients with multiple sclerosis.
MSRV is a retroviral element previously isolated in cell cultures from patients with multiple sclerosis. It is part of a new multi-copy endogenous retrovirus family named HERV-W and displays pro-inflammatory properties both in vitro in human PBMC cultures and in vivo in a humanized SCID mice model. In the present study, we have evaluated potential links between the pro-inflammatory properties of MSRV envelope protein and MS disease. Thus, cytokine productions mediated by the surface unit of MSRV envelope protein were evaluated in PBMC of MS patients and compared with healthy controls. Divergent reactivity to ENV-SU between MS and control PBMC was observed and was reflected by a significant increase of IFN-gamma, IL-6 and IL-12p40 production by the tested MS population. Interestingly, the overproduction of IL-6 and IL-12p40 was found to correlate with disease severity (EDSS) in most patients. Altogether our data suggest that MSRV envelope protein may induce an abnormal cytokine secretion, thus contributing to the inflammatory process in MS.
Rolland
Alexandre
A
Laboratoire d'Immunochimie, CEA/ INSERM-U548, 17 rue des Martyrs 38054 Grenoble, France.
Jouvin-Marche
Evelyne
E
Saresella
Marina
M
Ferrante
Pasquale
P
Cavaretta
Rosella
R
Créange
Alain
A
Marche
Patrice
P
Perron
Hervé
H
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004185:Disability Evaluation; D020077:Endogenous Retroviruses / Q000502:physiology*; D005260:Female; D015686:Gene Products, env / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000276:immunology* / Q000821:virology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D021122:Protein Subunits / Q000096:biosynthesis; D012720:Severity of Illness Index; D015854:Up-Regulation / Q000276:immunology; D014771:Virion / Q000502:physiology
D016207:Cytokines; D015686:Gene Products, env; D018836:Inflammation Mediators; D053762:Interleukin-12 Subunit p40; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D016753:Interleukin-10; D018664:Interleukin-12