Pathophysiology
Granulomatous inflammation is characterized primarily by accumulation of monocytes, macrophages and activated T-lymphocytes, with increased production of key inflammatory mediators, TNF-alpha, IFN-gamma, and IL-12, characteristic of a Th1-polarized response (T-helper lymphocyte-1 response). Sarcoidosis has paradoxical effects on inflammatory processes; it is characterized by increased macrophage and CD4 helper T-cell activation, resulting in accelerated inflammation, but immune response to antigen challenges such as tuberculin is suppressed. This paradoxic state of simultaneous hyper- and hypoactivity is suggestive of a state of anergy. The anergy may also be responsible for the increased risk of infections and cancer. The regulatory T-lymphocytes in the periphery of sarcoid granulomas appear to suppress IL-2 secretion, which is hypothesized to cause the state of anergy by preventing antigen-specific memory responses.
While TNF-alpha is widely believed to play an important role in the formation of granulomas, sarcoidosis can be triggered by treatment with the TNF-alpha antagonist etanercept.
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Sarcoidosis in a lymph node
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Asteroid body in sarcoidosis
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Micrograph showing pulmonary sarcoidosis with granulomas with asteroid bodies, H&E stain
Read more about this topic: Sarcoidosis