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To: keokalani'nui who wrote (13)	12/13/2001 10:05:20 PM
From: Miljenko Zuanic	Respond to of 214

This article may be good starting point to learn about immunity and CD. (Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1876.) © 2001 American Heart Association, Inc. -------------------------------------------------------------------------------- Brief Reviews Immune Mechanisms in Atherosclerosis Göran K. Hansson From the Center for Molecular Medicine and the Department of Medicine at Karolinska Hospital, Karolinska Institute, Stockholm, Sweden. Correspondence to Göran K. Hansson, Center for Molecular Medicine and Department of Medicine, Karolinska Hospital, Karolinska Institute, SE-17176, Stockholm, Sweden. E-mail Goran.Hansson@cmm.ki.se Atherosclerosis is an inflammatory disease. Its lesions are filled with immune cells that can orchestrate and effect inflammatory responses. In fact, the first lesions of atherosclerosis consist of macrophages and T cells. Unstable plaques are particularly rich in activated immune cells, suggesting that they may initiate plaque activation. We have seen a rapid increase in the understanding of the mechanisms that govern the recruitment, differentiation, and activation of immune cells in atherosclerosis. Experimental research has identified several candidate antigens, and there are encouraging data suggesting that immune modulation as well as immunization can reduce the progression of the disease. This review provides an overview of our current understanding of the role of immune mechanisms in atherosclerosis. Key Words: atherosclerosis • pathophysiology • cell biology • cytokines

To: keokalani'nui who wrote (13)	12/18/2001 2:04:58 AM
From: Miljenko Zuanic	Respond to of 214

jci.org J Clin Invest, December 2001, Volume 108, Number 12, 1825-1832 Copyright ©2001 by the American Society for Clinical Investigation -------------------------------------------------------------------------------- Article Therapeutic effect of neutralizing endogenous IL-18 activity in the collagen-induced model of arthritis Christine Plater-Zyberk1, Leo A.B. Joosten2, Monique M.A. Helsen2, Pascale Sattonnet-Roche1, Christiane Siegfried1, Sami Alouani1, Fons A.J. van de Loo2, Pierre Graber1, Shuki Aloni3, Rocco Cirillo4, Erik Lubberts2, Charles A. Dinarello5, Wim B. van den Berg2 and Yolande Chvatchko1 1 Serono Pharmaceutical Research Institute, Geneva, Switzerland 2 Rheumatology Research Laboratory, University Medical Center Nijmegen, Nijmegen, The Netherlands 3 InterPharma Laboratories, Nes Ziona, Israel 4 Istituto Di Ricerche Biomedche Antoine Marxer, Collereto Giacosa, Italy 5 Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA Address correspondence to: Yolande Chvatchko, Serono Pharmaceutical Research Institute 14, Chemin des Aulx CH-1228 Plan-les-Ouates, Geneva, Switzerland. Phone: 41-22-706-9792; Fax: 41-22-794-6965; E-mail: yolande.chvatchko@serono.com. Received for publication January 3, 2001, and accepted in revised form October 22, 2001. Two distinct IL-18 neutralizing strategies, i.e. a rabbit polyclonal anti-mouse IL-18 IgG and a recombinant human IL-18 binding protein (rhIL-18BP), were used to treat collagen-induced–arthritic DBA/1 mice after clinical onset of disease. The therapeutic efficacy of neutralizing endogenous IL-18 was assessed using different pathological parameters of disease progression. The clinical severity in mice undergoing collagen-induced arthritis was significantly reduced after treatment with both IL-18 neutralizing agents compared to placebo treated mice. Attenuation of the disease was associated with reduced cartilage erosion evident on histology. The decreased cartilage degradation was further documented by a significant reduction in the levels of circulating cartilage oligomeric matrix protein (an indicator of cartilage turnover). Both strategies efficiently slowed disease progression, but only anti–IL-18 IgG treatment significantly decreased an established synovitis. Serum levels of IL-6 were significantly reduced with both neutralizing strategies. In vitro, neutralizing IL-18 resulted in a significant inhibition of TNF-, IL-6, and IFN- secretion by macrophages. These results demonstrate that neutralizing endogenous IL-18 is therapeutically efficacious in the murine model of collagen-induced arthritis. IL-18 neutralizing antibody or rhIL-18BP could therefore represent new disease-modifying anti-rheumatic drugs that warrant testing in clinical trials in patients with rheumatoid arthritis.