Abstract: The present invention provides compositions and methods for upregulating IL-10 production in a stimulated cell. In one aspect, the invention provides methods of identifying ERK activating agents capable of activating and amplifying the ERK MAPK pathway in a cell. Such ERK activating agents are capable of upregulating the production of IL-10 in stimulated cells. In another aspect, the invention provides ERK activating agents identified by the screening methods of the invention. Methods are also provided for preventing and treating inflammation in a susceptible patient by administering to the patient, a therapeutically effective amount of an ERK activating agent identified in accordance with the invention.