Organ fibrosis and the basic inflammatory response
THE CONTEXT
Fibrosis in chronic disease shares mechanisms with cutaneous scar formation. Inflammation coordinates recognition and removal of injury, followed by regulation and repair.
Fibrosis in internal organs
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Although scar and fibrosis are often used interchangeably, fibrosis usually refers to abnormal collagen deposition in internal organs during chronic disease.
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The basic mechanisms of fibrosis are the same as those of skin scar formation during tissue repair.
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Persistent injurious stimuli, including chronic infections and immunologic reactions, induce fibrosis, which may cause substantial organ dysfunction or organ failure.
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TGF-b is the major cytokine involved in fibrosis. IL-13 produced by T lymphocytes may also contribute.
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Fibrotic disorders include liver cirrhosis, systemic sclerosis, idiopathic pulmonary fibrosis, pneumoconioses, drug- and radiation-induced pulmonary fibrosis, end-stage kidney disease, and constrictive pericarditis.
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The major functional impairment caused by fibrosis has prompted interest in developing antifibrotic drugs.
Components, causes, and recognition of inflammation
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Inflammation is a beneficial host response to foreign invaders and necrotic tissue, but it can also damage tissue.
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Its main components are a vascular reaction and a cellular response, activated by mediators derived from plasma proteins and various cells.
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Causes include infections, tissue necrosis, foreign bodies, trauma, and immune responses.
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Epithelial cells, tissue macrophages, dendritic cells, leukocytes, and other cells express receptors that detect microbes and necrotic cells. Circulating proteins recognize microbes in the blood.
Sequence and outcomes
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The five R’s are recognition of the injurious agent, recruitment of leukocytes, removal of the agent, regulation or termination of the response, and repair.
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Acute inflammation may eliminate the noxious stimulus, followed by decline of the reaction and tissue repair.
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Persistent injury may instead lead to chronic inflammation.