Abstract: Agents with integrin-afffecting activity, including antibodies and molecules having the antigen-binding portion of such antibodies, are used to regulate inflammatory mediators, including TL-1&bgr;, IL-6, IL-8, nitric oxide, PGE2 and MMPs.

Abstract: The invention is a method of inhibiting the production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo biological system. The method employs a tetracycline compound to inhibit the production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the biological system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.

Abstract: A method is disclosed for inhibiting endogenous production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo mammalian system. The method employs a tetracycline compound to inhibit production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the mammalian system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.

Abstract: An novel isoform of inducible nitric oxide synthase (OA-NOS) has been identified in osteoarthritis-affected articular cartilage. Some properties, including molecular weight, are similar to the constitutive isoform of neuronal nitric oxide synthase (ncnos) while other properties share similarity with the previously identified inducible nitric oxide (iNOS). Acetylating agents, such as aspirin and N-acetylimidazole act on both iNOS and OA-NOS by inhibiting their catalytic activities. A method is provided to screen for acetylating agents that inhibit OA-NOS, and the selective inhibition of OA-NOS by inhibitory agents is determined by comparison to a panel of different isoforms of nitric oxide synthase.