Chronic inflammation, systemic effects, and tissue regeneration
THE CONTEXT
Persistent inflammatory stimuli produce chronic cellular responses and scarring. Inflammation also has systemic effects, while tissue regeneration depends on the proliferative capacity of surviving cells.
Chronic and granulomatous inflammation
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Chronic inflammation is a prolonged response to persistent stimuli, including microbes that resist elimination, immune responses against self or environmental antigens, and toxic substances such as silica.
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Inflammation, tissue injury, attempted repair by scarring, and immune responses coexist.
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The cellular infiltrate includes macrophages, lymphocytes, plasma cells, and other leukocytes.
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Macrophage and lymphocyte cytokines, notably those produced by T lymphocytes, mediate the response. Bidirectional interactions between these cells amplify and prolong inflammation.
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Granulomatous inflammation develops through T cell and macrophage activation against agents resistant to eradication. It features aggregates of macrophages with epithelioid morphology.
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Causes of granulomatous inflammation listed in the source include tuberculosis, fungal infections, and syphilis.
Systemic inflammatory effects
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TNF and IL-1 stimulate hypothalamic prostaglandin production, causing fever.
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Leukocytosis results from release of bone marrow cells. Colony-stimulating factors also stimulate leukocyte production from marrow precursors.
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IL-6 and other cytokines act on liver cells to stimulate acute-phase protein synthesis, including C-reactive protein.
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In severe infections, high levels of TNF and other cytokines can induce septic shock, with falling blood pressure, disseminated intravascular coagulation, and metabolic abnormalities.
Regenerative capacity
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Continuously dividing cells occur in epithelia and hematopoietic tissues. Normally quiescent cells capable of proliferation occur in most parenchymal organs. Neurons and skeletal and cardiac muscle are listed as nondividing cells.
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A tissue’s regenerative capacity depends on the proliferative potential of its constituent cells.
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Growth factors and interactions with the extracellular matrix stimulate cell proliferation.
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Liver regeneration is triggered by cytokines and growth factors produced in response to loss of liver mass and inflammation. Depending on the situation, repair occurs through proliferation of surviving hepatocytes or differentiation of stem cells.