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C-reactive protein (CRP) is an acute phase reactant commonly measured in clinical practice as a marker of inflammation and to monitor disease severity, disease course and treatment response. It should not be confused with protein C (an anticoagulant) or C-peptide (a component of proinsulin).
Cellular injury, infection or neoplasia results in the up-regulation and expression of various cytokines and chemical mediators. Interleukin-6 causes the downstream transcription and production of C-reactive protein in hepatocytes 1.
CRP is important in binding to damaged or injured cellular components (e.g. damaged cell membranes) and pathogen components (e.g. bacterial cell wall proteins) and potently activates the classical complement pathway through binding C1q 2,3.
Synthesis of C-reactive protein commences soon after a stimulus and levels can reach above 5 mg/L in 6 hours and usually peak around the 48 hour mark. The half-life of C-reactive protein is 19 hours and this rate is constant in both diseased and healthy states. The total level of C-reactive protein is therefore determined by the strength and continued presence of the stimulating infection or injury 4. This makes levels useful to track disease.
The normal plasma level of CRP is between 0.8 and 3.0 mg/L 4. CRP levels in asymptomatic patients increase with age, possibly due to the increased prevalence of undiagnosed pathology (e.g. cancer) 5. CRP levels are relatively stable between individuals and from day to day in the absence of disease 4,5. CRP can become drastically elevated by a factor of one hundred to one thousand to over 500 mg/L 1.
CRP is very sensitive for detecting inflammation, cellular injury, neoplasia and infection, it however is non-specific and numerous conditions elevate it. A short (and non-exhaustive) list is provided below 1.
- infection: bacterial (e.g. pneumonia), viral (e.g. viral respiratory tract infection), mycobacterial (e.g. tuberculosis), fungal (e.g. pulmonary candidiasis)
- autoimmune disease: Crohn disease, rheumatoid arthritis, juvenile idiopathic arthritis, vasculitis, autoimmune hepatitis
- cellular injury: myocardial infarction, acute pancreatitis
- trauma: burns, post-surgery
- malignancy: lymphoma, solid organ tumors (e.g. colon adenocarcinoma)
Absent or minor elevation
The following conditions do not usually result in substantially elevated C-reactive protein levels: scleroderma, SLE, dermatomyositis, ulcerative colitis, and leukemia. This fact may be useful in distinguishing between certain diseases 1.
Studies have shown that healthy pregnant females have slightly higher CRP levels than healthy non-pregnant women. However it is not normal to be markedly elevated, in which case it should be treated in the same way as in a non-pregnant patient, and assumed to be bacterial infection in the first instance 7,8.
History and etymology
C-reactive protein was named due to its ability to precipitate the C-polysaccharide present in Streptococcus pneumonia 1.