TREATMENT OF VASCULAR LEAKAGE SYNDROME AND COLLAGENASE INDUCED DISEASE BY ADMINISTRATION OF MATRIX METALLOPROTEINASE INHIBITORS

摘要

A method for identifying patients at risk of developing vascular leakage syndrome and systemic inflammatory response syndrome (SIRS) such as septic shock by determining the serum levels of metalloproteinase expression, in particular type IV collagenase expression, as well as a method of treating or preventing vascular leakage syndrome and SIRS by the administration of one or more metalloproteinase inhibitors, preferably type IV collagenase inhibitors is taught. Additionally, the therapeutic efficacy of bis(dioxopiperazine) compounds is determined on the basis of collagenase inhibiting activity, and the compounds which inhibit collagenase activity are utilized for the treatment of collagenase related disorders, e.g., vascular leakage syndrome, septic shock, stroke, cardiac disorders, angiogenesis, and arthritis. Finally, a method for preventing or treating toxicity caused by endogenous cytokine expression or cytokine administration by the administration of one or more metallo-proteinase inhibitors, preferably type IV collagenase inhibitors is taught.