University of Pittsburgh

North Shore-Long Island Jewish Research Institute

Luis Ulloa

Kevin J Tracey

Mitchell P Fink

Russell L Delude

This invention is directed to a method of using a therapeutic composition comprising a compound of an alpha-ketoalkanoic acid (pyruvate) and/or its derivatives for the treatment of cytokine-mediated inflammatory conditions. The compound is an alpha-ketoalkanoic acid, a physiologically acceptable salt of an alpha-ketoalkanoic acid, an ester of an alpha-ketoalkanoic acid, or an amide of an alpha-ketoalkanoic acid. A component for inducing and stabilizing the enol resonance form of the ester at physiological pH values is also disclosed. The cytokine-mediated inflammatory conditions are mediated by, for example, an 'early' (Tumor Necrosis Factor (TNF), interleukin-1&#x3b2; (IL-1&#x3b2;)) or 'late' (high mobility group B-1 (HMGB-1)) mediator of inflammation. Exemplary cytokine-mediated inflammatory conditions include, but are not limited to, local and systemic inflammation, inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatoid arthritis, asthma (including status asthmaticus), sepsis or septic shock, also including inflammatory skin conditions, for example, psoriasis and eczema.

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Jackson Heights, NY, United States of America

Luis Ulloa