Abstract: Methods compositions and combinations for treating various diseases and conditions that are induced by cytokine activation and response, such as sepsis are provided. The method comprises orally administering a therapeutically effective amount of protease to a mammal to increase the inactivation of cytokines, such as TNF-alpha and INF-gamma. The composition comprises any pharmaceutically acceptable protease, for example, plant and microbial proteases may be used. The composition may be given, for example, singly or in combination with vitamins, minerals, antioxidants, bioflavonoids proanthocyanidins, herbs, herbal extracts, plant and animal concentrates, and non-prescriptive analgesics.

Abstract: A method for treating various diseases and conditions that are dependent on activated &agr;2 macroglobulin in the blood and extravascular tissue is disclosed. The method comprises orally administering a therapeutically effective amount of protease to a mammal to increase the amount of activated &agr;2 macroglobulin, which in turn enhances the clearance of TNF-&agr;, leptin, and &bgr;-amyloid while enhancing delivery of TGF-&bgr;. The protease may be any pharmaceutically acceptable protease, and preferably is of microbial and/or plant origin, given singly or in combination with vitamins, minerals, antioxidants, bioflavonoids, proanthocyanidins, herbs, herbal extracts, plant and animal concentrates, and non-prescription analgesics. The microbial protease is preferably administered in a total daily dosage of at least 100,000 HUT (or equivalent biological activity). The plant protease component is preferably administered in a total daily dosage of at least 50,000 PU (or equivalent biological activity).