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.