What Models of Granulomatous Inflammation Provide the Immunologist

Granulomas usually serve to protect the host from the spread of persistent microorganisms or other enduring injurious substances. They are complex inflammatory reactions that use many immune mechanisms to control the inciting nudis. These lesions can persist for weeks, months, or even years. Thus, understanding the mechanisms that enhance, diminish, or modulate granulomas could aid in the treatment of many diseases. Moreover, experimental animal models of granulomatous inflammation allow sophisticated investigation of some disease processes not possible using human subjects. Granulomatous inflammations are chronic, composed of activated leukocytes that are selected for deposition at the site of injury. They use various effector mechanisms, delicately balanced by many immunoregulatory circuits. Under some experimental conditions, granulomas can be isolated readily from host tissue and subjected to sophisticated immunological analysis. Therefore, it is possible to dissect the actual, local control mechanisms that govern the granulomatous response. Lesions learned studying granulomas are applicable to other types of inflammation, since granulomas use immunoregulatory networks and soluble cytokines common to many inflammatory states. Using these experimental models, it is readily apparent that studies utilizing splenocytes or peripheral blood leukocytes may not reveal the true, dominant immunoregulatory mechanisms employed at sites of active inflammation. The leukocytes of spleens and blood are a mixture of cells in various stages of activation, many of which are not destined to participate in a selective immune response. Also, granulomas are sustained inflammatory reactions permitting analysis of the unique features of chronic maintenance, as opposed to acute phase inflammation.