Cytokines and murine autoimmune encephalomyelitis: inhibition or enhancement of disease with antibodies to select cytokines, or by delivery of exogenous cytokines using a recombinant vaccinia virus system.
To examine the complex role of cytokines in the pathogenesis of actively induced murine EAE we measured the levels of a number of cytokines (IL-6, IFN gamma and TNF) in the spinal cord and CSF of mice with active experimental autoimmune encephalomyelitis (EAE) and found them all to be elevated. We next treated mice with antibodies to these three cytokines, which were over expressed in the CNS, to determine if they would alter disease and found the following: anti-IL-6 had no significant effect on disease, anti-IFN gamma exacerbated disease, and anti-TNF either enhanced, had no effect or inhibited EAE depending on the antibody used. We then treated mice with exogenous cytokines, delivered using a recombinant vaccinia virus system, and found that the IL-6 and TNF virus constructs inhibited EAE whereas the IFN gamma construct had no effect on disease. Other cytokine recombinant viruses were also tested and it was found that the IL-1 beta, IL-2 and IL-10 viruses inhibited EAE while an IL-4 virus either had no effect or enhanced disease. We do not know the mechanism of action of the various cytokines in this system, but irrespective of the mechanism(s), this work clearly demonstrates that delivery of select cytokines using recombinant virus-cytokine constructs can provide a powerful means of down-regulating experimental organ-specific autoimmune disease.
Willenborg
D O
DO
Neurosciences Research Unit, Woden Valley Hospital, Canberra, Australia.
Fordham
S A
SA
Cowden
W B
WB
Ramshaw
I A
IA
D000818:Animals; D016207:Cytokines / Q000008:administration & dosage / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000134:cerebrospinal fluid / Q000378:metabolism; D015850:Interleukin-6 / Q000134:cerebrospinal fluid / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage; D013116:Spinal Cord / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000378:metabolism; D014616:Vaccinia virus
D016207:Cytokines; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma