Combined treatment of acute EAE in Lewis rats with TNF-binding protein and interleukin-1 receptor antagonist.
Experimental autoimmune encephalomyelitis (EAE) is a term given to describe a collection of animal models representing the human disease multiple sclerosis (MS). Although not fully understood, the involvement of cytokines and the immune system in either EAE or human MS is well established. Past efforts have shown that inhibition of proinflammatory cytokines tumor necrosis factor (TNF-alpha) or interleukin-1 (IL-1) result in amelioration of acute EAE in Lewis rats. The present study examined this model for the effect of concomitant inhibition of both TNF-alpha and IL-1, which resulted in a modest but significant therapeutic effect that was superior to inhibition of either single agent alone with respect to four of the five variables used to follow the progression of disease in this model, i.e., clinical severity, frequency of disease, loss of body weight, and day of onset. These results are in accordance with the idea that combination treatments are likely to prove superior to single agent therapy in the treatment of autoimmune inflammatory disease.
Wiemann
B
B
Department of Pharmacology, Amgen, Inc., Thousand Oaks, California 91320-1789, USA.
Van
G Y
GY
Danilenko
D M
DM
Yan
Q
Q
Matheson
C
C
Munyakazi
L
L
Ogenstad
S
S
Starnes
C O
CO
D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D019281:Dimerization; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D011092:Polyethylene Glycols; D051381:Rats; D011917:Rats, Inbred Lew; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D016029:Receptors, Very Late Antigen / Q000276:immunology; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000627:therapeutic use*; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
C507763:IL1RN protein, human; D039041:Integrin alpha4beta1; D016023:Integrins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D018124:Receptors, Tumor Necrosis Factor; D016029:Receptors, Very Late Antigen; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D011092:Polyethylene Glycols