Acute-phase proteins and systemic manifestations of inflammation
THE CONTEXT
Systemic inflammation alters blood cell counts, induces hepatic plasma protein synthesis, and produces metabolic and constitutional effects.
Blood cell changes
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Some allergies and parasitic infestations increase circulating eosinophils, producing eosinophilia.
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Typhoid fever, rickettsial infections, and certain viral and protozoal infections can decrease circulating white cells, producing leukopenia.
Acute-phase response
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Acute-phase proteins are mostly synthesized in the liver. Their blood levels may increase several hundred-fold in response to inflammatory stimuli, with cytokines stimulating their synthesis in hepatocytes.
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Examples include C-reactive protein (CRP), fibrinogen, and serum amyloid A (SAA).
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CRP and SAA bind microbial cell walls and may contribute to host defense by acting as opsonins and fixing complement.
Diagnostic and chronic effects
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Fibrinogen neutralizes the negative surface charge of red cells, promoting stacks called rouleaux. These sediment faster than individual cells, providing the basis for measuring the erythrocyte sedimentation rate to detect inflammation.
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Prolonged acute-phase protein production, especially SAA, during chronic inflammation can cause amyloidosis.
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Elevated serum CRP has been proposed as a marker of increased myocardial infarction risk in patients with coronary artery disease.
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Inflammation increases production of hepcidin, an iron-regulating peptide that reduces iron availability and is responsible for anemia associated with chronic inflammation.
Other systemic manifestations
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Systemic responses include increased heart rate and blood pressure, rigors, chills, anorexia, somnolence, and malaise.
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Sweating decreases mainly because blood flow shifts from cutaneous to deep vascular beds, minimizing heat loss through the skin.
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Constitutional symptoms probably reflect cytokine actions on brain cells.
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In severe bacterial infections, bacteria and their products in the blood stimulate enormous quantities of cytokines, notably TNF, IL-1, and IL-6.