International Immunology, Vol 9, 1517-1522, Copyright © 1997 by Oxford University Press
L Cahalon, O Lider, H Schor, A Avron, D Gilat, R Hershkoviz, R Margalit, A Eshel, O Shoseyev and IR Cohen
Inflammation is the clinical expression of chemical mediators such as the
pro-inflammatory cytokine tumor necrosis factor (TNF-)-alpha produced by
macrophages and other cells activated in the immune response. Hence, agents
that can inhibit TNF-alpha may be useful in treating arthritis and other
diseases resulting from uncontrolled inflammation. We now report that the
cleavage of heparin by the enzyme heparinase I generates sulfated
disaccharide (DS) molecules that can inhibit the production of TNF-alpha.
Administration of nanogram amounts of the sulfated DS molecules to
experimental animals inhibited delayed- type hypersensitivity to a skin
sensitizer and arrested the joint swelling of immunologically induced
adjuvant arthritis. Notably, the sulfated DS molecules showed a bell-shaped
dose-response curve in vitro and in vivo: decreased effects were seen using
amounts of the DS molecules higher than optimal. Thus, molecular regulators
of inflammation can be released from the natural molecule heparin by the
action of an enzyme.
ARTICLES
Heparin disaccharides inhibit tumor necrosis factor-alpha production by macrophages and arrest immune inflammation in rodents
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
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