Exp Neurol 2001 Dec;172(2):460-8
Espejo C, Penkowa M, Saez-Torres
I, Xaus J, Celada A, Montalban X, Martinez-Caceres EM.
Unitat de Neuroimmunologia Clinica,
Hospital Vall d'Hebron, Barcelona, 08035, Spain
The role of interferon-gamma (IFN-gamma) in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still controversial.
We have studied the function of IFN-gamma and its receptor in the EAE model using two different IFN-gamma receptor knockout (IFN-gamma R(-/-)) mouse types: C57Bl/6x129Sv, with a disruption of the IFN-gamma receptor cytoplasmic domain, and 129Sv, homozygous for a disrupted IFN-gamma receptor gene.
Mice were immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein.
A subgroup of mice was treated with anti-IFN-gamma monoclonal antibodies (mAb) on day 8 postimmunization.
Clinical scoring and both histological and immunohistochemical studies were undertaken for all groups.
We hereby show that treatment with anti-IFN-gamma mAb worsened the disease course of 129Sv wild-type mice.
However, it decreased the mean daily score in IFN-gamma R(-/-) 129Sv and the incidence of the disease down to 50% in C57Bl/6x129Sv IFN-gamma R(-/-) mice.
Moreover, after anti-IFN-gamma mAb treatment, oxidative stress levels, metallothionein I and II antioxidant protein expression, and apoptoticneuronal death were increased in wild-type mice while decreased in IFN-gamma R(-/-) mice.
These results suggest a putative
alternative mechanism of action of this cytokine that works independent
of its receptor.
PMID: 11716570 [PubMed - in process]
(c) 2001 Elsevier Science