C-Reactive Protein (CRP) is a pentameric protein synthesized primarily by the liver in response to tissue injury, infection, or inflammation. As an acute phase reactant, its concentration in the bloodstream changes rapidly and dramatically as part of the body’s immediate, non-specific defensive reaction. The “acute phase response” is the systemic reaction to a disturbance of the body’s stability, and the measurement of CRP is a widely used biomarker for detecting this process.
The Acute Phase Response and CRP’s Biological Function
The cascade that leads to the production of C-Reactive Protein begins at the site of tissue damage or pathogen invasion. Cells at this location release signaling molecules called cytokines, which act as chemical messengers to initiate the systemic inflammatory response. Interleukin-6 (IL-6) is the most powerful and direct of these cytokines, traveling through the bloodstream to the liver.
Upon reaching the liver, IL-6 binds to receptors on liver cells, triggering the transcription and massive synthesis of the CRP gene. This process causes the concentration of CRP in the blood to increase rapidly, often rising within six to twelve hours of the initial stimulus. CRP levels can increase by up to 1,000-fold in cases of severe inflammation or infection, marking it as a highly sensitive indicator of an active process.
Once in the circulation, the primary biological role of CRP is to participate in the innate immune system’s defense and clearance mechanisms. CRP functions as an opsonin, tagging foreign or damaged materials for destruction. It binds to specific molecules on the surface of pathogens, such as the phosphorylcholine component of pneumococcal C-polysaccharide, or to damaged cell membranes. This binding activates the classical pathway of the complement system, a complex network of proteins that helps destroy invaders and clear debris. The tagged materials are then efficiently recognized and engulfed by phagocytic immune cells, like macrophages, facilitating their removal.
Clinical Measurement and Interpretation of CRP Levels
The standard CRP test measures the dramatic elevations characteristic of the acute phase response. A typical reference range for a healthy individual is generally below 0.9 mg/dL or 10 mg/L. The test confirms the presence of significant inflammation, though it cannot pinpoint the exact cause or location.
A moderate elevation is considered to be a CRP level between 1.0 mg/dL and 10.0 mg/dL, which may be associated with systemic inflammation from conditions such as rheumatoid arthritis, mild infection, or malignancy. Markedly elevated CRP levels, often exceeding 10 mg/dL, indicate a significant, active acute process. In severe cases, such as major bacterial infections or extensive tissue trauma, levels can rise into the hundreds of milligrams per liter.
Conditions that cause acute spikes include major bacterial infections like sepsis or pneumonia, severe tissue trauma such as burns or extensive surgery, and acute flare-ups of chronic conditions like inflammatory bowel disease. Clinicians use the magnitude of the rise to help distinguish between viral and bacterial infections, as bacterial infections typically trigger a much higher and more rapid CRP increase. A high CRP level is also used to monitor the progress of a disease, as a decreasing level suggests that the inflammation is subsiding and the patient is responding to therapy.
Standard Versus High-Sensitivity CRP
It is important to distinguish between the two different ways C-Reactive Protein is measured. The “Standard CRP” test, used to assess acute inflammation, is calibrated to measure the high concentrations (often above 10 mg/L) that occur during an acute phase response. The focus of this test is to detect and monitor severe inflammatory events.
The “High-Sensitivity CRP” (hs-CRP) test is engineered to detect much lower concentrations of the protein, often measuring down to 0.3 mg/L. This enhanced sensitivity allows the hs-CRP test to detect chronic, low-grade inflammation that the standard CRP test would miss. The clinical purpose of the hs-CRP test is distinct from acute diagnostics.
The hs-CRP test is primarily used as a predictive tool for assessing cardiovascular risk. Persistently low-level inflammation in the blood vessels is a factor in the development of atherosclerosis, which leads to heart disease. Levels are typically interpreted in categories: an hs-CRP level below 1.0 mg/L indicates low cardiovascular risk, while levels over 3.0 mg/L suggest a high risk. This measurement is generally taken when the patient is in a metabolically stable state, ensuring the result is not artificially elevated by an acute infection.