Distinct roles for IP-10/CXCL10 in three animal models, Theiler's virus infection, EAE, and MHV infection, for multiple sclerosis: implication of differing roles for IP-10.
Theiler's murine encephalomyelitis virus (TMEV) causes demyelination with inflammation of the central nervous system (CNS) in mice and is used as an animal model for multiple sclerosis (MS). Interferon-gamma inducible protein-10 kDa (IP-10) is a CXC chemokine and a chemoattractant for CXCR3+ T cells. IP-10 mRNA is expressed in the CNS during TMEV infection. However, administration of anti-IP-10 serum caused no difference in clinical signs, inflammation, demyelination, virus persistence or anti-virus antibody response in TMEV infection, while levels of virus specific and autoreactive lymphoproliferation increased. This likely reflects a difference in the pathogenesis of TMEV infection from that of two other animal models for MS, mouse hepatitis virus infection and experimental allergic encephalomyelitis (EAE), where blocking of IP-10 resulted in clinical and histological improvement with suppression of antigen specific lymphoproliferation. In this review, we compare and contrast the roles of IP-10 between the three animal models for MS, and discuss the relevance to MS patients with different clinical courses.
Tsunoda
Ikuo
I
Department of Neurology, University of Utah School of Medicine, 30 North 1900 East, Salt Lake City, UT 84132-2305, USA.
Lane
Thomas E
TE
Blackett
Jana
J
Fujinami
Robert S
RS
D000818:Animals; D018188:Cardiovirus Infections / Q000503:physiopathology*; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000378:metabolism*; D018352:Coronavirus Infections / Q000503:physiopathology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis; D006517:Murine hepatitis virus; D017945:Theilovirus
D054357:Chemokine CXCL10; D019743:Chemokines, CXC