Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
J Neuroimmunol ; 182(1-2): 135-52, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17126916

ABSTRACT

Rhesus monkeys immunized with MOG(34-56), a dominant T-cell epitope from myelin/oligodendrocyte glycoprotein, develop an acute neurological disease resembling acute disseminated encephalomyelitis (ADEM) in humans. The typical large demyelinated lesions and mononuclear infiltrates in the monkey brains are caused by MOG(34-56) T-cells. We show that MOG(34-56)-reactive CD4+ and CD8+ T-cells are induced in monkeys immunized with a peptide from the human CMV major capsid protein (UL86; 981-1003), that shares sequence similarity with MOG(34-56). Monkeys sensitized against the viral peptide and subsequently challenged with MOG(34-56) display histological signs of encephalitis, but do not show overt neurological signs.


Subject(s)
Capsid Proteins/immunology , Cholesterol/analogs & derivatives , Encephalomyelitis, Autoimmune, Experimental/immunology , Epitopes, T-Lymphocyte/immunology , Glycoproteins/immunology , Macaca mulatta/immunology , Peptide Fragments/immunology , Animals , Antibodies/blood , Brain/pathology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Capsid Proteins/pharmacology , Cell Line , Cell Proliferation/drug effects , Cholesterol/immunology , Cross Reactions , Encephalomyelitis, Autoimmune, Experimental/pathology , Encephalomyelitis, Autoimmune, Experimental/physiopathology , Female , Humans , Lymphocyte Activation , Male , Monocytes/pathology , Myelin Proteins , Myelin-Associated Glycoprotein/immunology , Myelin-Associated Glycoprotein/pharmacology , Myelin-Oligodendrocyte Glycoprotein , Peptide Fragments/pharmacology , Polyethylene Glycols , Recombinant Proteins/immunology , Spinal Cord/pathology
2.
Arthritis Rheum ; 52(2): 627-36, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15693002

ABSTRACT

OBJECTIVE: Collagen-induced arthritis (CIA) in the rhesus monkey is a nonhuman primate model of rheumatoid arthritis (RA). The close phylogenetic relationship between humans and the rhesus monkey makes this model useful for the preclinical safety and efficacy testing of new therapies that are inactive in animals more distinctly related to humans. In this study, we tested the therapeutic potential of a novel, small molecular weight antagonist of CCR5, SCH-X, in this model. METHODS: CIA was induced in 10 rhesus monkeys. The animals were allocated to receive SCH-X or saline as the control (n = 5 in each group). Treatment was initiated on the day of CIA induction and continued for 45 days. Monkeys were monitored before and 63 days after CIA induction for macroscopic signs of clinical arthritis, such as soft-tissue swelling and body weight. Furthermore, markers of inflammation and joint degradation were monitored to follow the disease course. RESULTS: Only 2 of 5 animals in the SCH-X-treated group displayed prominent soft-tissue swelling, compared with all 5 saline-treated monkeys. In addition to the suppression of joint inflammation, treatment with SCH-X resulted in a reduction in joint destruction, as demonstrated by lower rates of urinary excretion of collagen crosslinks, with confirmation by histology. Whereas in all saline-treated monkeys, marked erosion of joint cartilage was observed, this was absent in 4 of the 5 SCH-X-treated monkeys. CONCLUSION: The systemic effects of treatment with SCH-X were a suppressed acute-phase reaction (reduction in C-reactive protein level) in the 3 treated monkeys with CIA that remained asymptomatic, and an altered antibody response toward type II collagen. The results suggest that the CCR5 antagonist SCH-X might have a strong clinical potential for treatment during periods of active inflammation, as seen in RA.


Subject(s)
Arthritis, Experimental/prevention & control , CCR5 Receptor Antagonists , Animals , Arthritis, Experimental/chemically induced , Arthritis, Experimental/pathology , Cartilage, Articular/pathology , Collagen Type II , Follow-Up Studies , Macaca mulatta , Male
SELECTION OF CITATIONS
SEARCH DETAIL
...