Causes of chronic inflammation include the following:
· Following a bout of acute inflammation
· Persistent infections
· Infections with certain organisms, including viral infections, mycobacteria, parasitic infections, and fungal infections
· Autoimmune diseases
· Response to foreign material
· Response to malignant tumors
There are several important cells in chronic inflammation.
· Macrophages are derived from blood monocytes. Tissue-based macrophages(life span in connective tissue compartment is 60–120 days) are found in connec-tive tissue (histiocyte), lung (pulmonary alveolar macrophages), liver (Kupffer cells), bone (osteoclasts), and brain (microglia). During inflammation circu-lating monocytes emigrate from the blood to the periphery and differentiate into macrophages.
Respond to chemotactic factors: C5a, MCP-1, MIP-1α, PDGF, TGF-β
Secrete a wide variety of active products (monokines)
May be modified into epithelioid cells in granulomatous processes
· Lymphocytes include B cells and plasma cells, as well as T cells. Lymphotaxinis the lymphocyte chemokine.
· Eosinophils play an important role in parasitic infections and IgE-mediatedallergic reactions. The eosinophilic chemokine is eotaxin. Eosinophil granules contain major basic protein, which is toxic to parasites.
· Basophils contain similar chemical mediators as mast cells in their granules.Mast cells are present in high numbers in the lung and skin. Both basophils and mast cells play an important role in IgE-mediated reactions (allergies and anaphylaxis) and can release histamine.
Chronic granulomatous inflammation is a specialized form of chronic inflamma-tion characterized by small aggregates of modified macrophages (epithelioid cells and multinucleated giant cells) usually populated by CD4+ Th1 lymphocytes.
Composition of a granuloma is as follows:
· Epithelioid cells, located centrally, form when IFN-γ transforms macrophages to epithelioid cells. They are enlarged cells with abundant pink cytoplasm.
· Multinucleated giant cells, located centrally, are formed by the fusion of epi-thelioid cells. Types include Langhans-type giant cell (peripheral arrangement of nuclei) and foreign body type giant cell (haphazard arrangement of nuclei).
· Lymphocytes and plasma cells are present at the periphery.
· Central necrosis occurs in granulomata due to excessive enzymatic breakdown and is commonly seen in Mycobacterium tuberculosis infection as well as fun-gal infections and a few bacterial infections. Because of the public health risk of tuberculosis, necrotizing granulomas should be considered tuberculosis until proven otherwise.
Granulomatous diseases include tuberculosis (caseating granulomas), cat-scratchfever, syphilis, leprosy, fungal infections (e.g., coccidioidomycosis), parasitic infec-tions (e.g., schistosomiasis), foreign bodies, beryllium, and sarcoidosis.