What is C-Reactive Protein?
C-reactive protein (CRP) is an acute-phase protein synthesized exclusively by the liver in response to inflammatory cytokines (particularly IL-6) that serves as a biomarker of systemic inflammation and plays an active role in the innate immune response. 1
Fundamental Biology and Structure
CRP is a pentameric protein belonging to the ancient pentraxin family, arranged in a cyclic homopentameric structure that is evolutionarily conserved across vertebrates and many invertebrates. 2, 3
The protein functions as a pattern recognition molecule, binding to specific molecular configurations typically exposed during cell death or found on pathogen surfaces, particularly phosphocholine present in bacterial membranes, cell membranes, and lipoproteins. 2, 4
CRP participates in innate immunity through multiple mechanisms: it opsonizes pathogens, activates the complement system through the classical pathway (generating C3 but not C5 convertase), and binds to immunoglobulin G receptors. 4, 3
Production and Kinetics
Synthesis begins 4-6 hours after an inflammatory insult, with CRP concentration doubling every 8 hours and reaching peak levels at 36-50 hours after the initial stimulus. 1, 5
The sole determinant of plasma CRP levels is its hepatic synthesis rate, which is directly proportional to the intensity of the inflammatory insult—levels can rise from normal (<3 mg/L) to above 500 mg/L during acute illness. 1
Production and elimination are not influenced by renal replacement therapy or immunosuppression (including systemic steroids and neutropenia), making it a reliable marker across diverse clinical contexts. 5, 1
Clinical Significance
Cardiovascular Disease
The American Heart Association recognizes CRP as an independent predictor of cardiovascular events, with high-sensitivity CRP (hs-CRP) being the best inflammatory biomarker for detecting enhanced absolute risk of cardiovascular disease in the general population. 5, 1
CRP may be directly involved in atherothrombogenesis beyond its role as an inflammatory marker, with elevated levels predicting all-cause and cardiovascular mortality in both hemodialysis and peritoneal dialysis patients. 5, 1
Surgical and Infectious Applications
CRP demonstrates 68-92% sensitivity and 40-67% specificity as a marker of bacterial infection, though its low specificity limits diagnostic value when used in isolation since it cannot differentiate bacterial infections from non-infectious causes of inflammation. 5, 1
In postoperative monitoring, CRP below 75 mg/L on postoperative day 3 suggests uncomplicated recovery and may serve as a safe discharge criterion, while CRP above 215 mg/L on postoperative day 3 predicts complications requiring investigation. 5, 1
Exercise and Athletic Context
CRP shows a delayed response to exercise, with levels typically not increasing immediately but rising significantly 24 hours post-exercise, with one study showing a 152-fold increase after ultradistance running lasting more than 24 hours. 5
Long-term physical activity leads to decreased resting CRP levels through reduced cytokine production, while exhaustive resistance training over several weeks can lead to chronic CRP increases. 5
Critical Limitations
CRP cannot differentiate between bacterial infection, viral infection, tissue injury, chronic inflammatory conditions, or malignancy without clinical context—elevated CRP (>10 mg/L) in patients with apparent allergic symptoms should prompt consideration of alternative diagnoses such as bacterial infection or inflammatory diseases. 1, 6
Absolute CRP values must be interpreted in context of the clinical scenario, baseline patient factors (age, sex, race, obesity, smoking status), and temporal trends rather than as standalone diagnostic criteria. 1, 7
CRP should be used as an additional tool that aids clinical observation and physical examination but cannot replace it, and serial testing should not be used to monitor treatment effects as treatment should target the underlying cause rather than the CRP level itself. 1, 7