Evaluation of granulomas and systemic inflammatory responses
THE CONTEXT
Granulomas narrow the possible causes of inflammation, while cytokines can produce systemic reactions even when inflammation is localized.
Identifying the cause of granulomas
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Tuberculosis is the prototype infectious granulomatous disease and should always be excluded when granulomas are identified.
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Syphilis and some fungal infections can also cause granulomatous inflammation. Immune-mediated causes include Crohn disease and sarcoidosis.
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Morphology may suggest a diagnosis, but the specific etiologic agent must be identified in the clinical laboratory.
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Methods include special stains, such as acid-fast stains for Mycobacterium tuberculosis, microbial culture, molecular techniques, and serologic studies, such as those used for syphilis.
Mediators of systemic inflammation
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Even localized inflammation can cause cytokine-induced systemic reactions.
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Bacterial products such as LPS and other inflammatory stimuli induce cytokine production. TNF, IL-1, and IL-6 are important systemic mediators; type I interferons also contribute.
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Systemic reactions are typically more severe in acute inflammation than in chronic inflammation, reflecting the levels of cytokine production.
Fever pathway
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Fever is a prominent systemic manifestation, especially when inflammation accompanies infection. Fever-inducing substances are called pyrogens.
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Bacterial products such as LPS stimulate leukocytes to release IL-1 and TNF. These cytokines increase prostaglandin production, particularly PGE2, in vascular and perivascular cells of the hypothalamus.