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Choosing an Inflammation Marker: hs-CRP, PCT and IL-6

hs-CRP, procalcitonin and interleukin-6 report different aspects of the inflammatory response. A guide to selecting the right analyte.

Three Markers, Three Signals

hs-CRP, procalcitonin (PCT) and interleukin-6 (IL-6) are not competing versions of one measurement. C-reactive protein is an acute-phase protein produced by the liver, and high-sensitivity CRP detects the low-grade elevations associated with cardiovascular risk assessment. PCT is a peptide precursor whose concentration rises with certain bacterial infections. IL-6 is a cytokine that rises earlier in the inflammatory cascade. Each reflects a different point in the response, so the choice of marker depends on the question being asked.

Where Each Marker Is Useful

hs-CRP is used to assess chronic low-grade inflammation and to support cardiovascular risk stratification. PCT has been studied as an aid in distinguishing bacterial from non-bacterial inflammation and is used in some settings to inform antibiotic decisions. IL-6 rises rapidly after an inflammatory stimulus and can be measured in serum, plasma and cell culture, which makes it useful in both clinical research and basic immunology. The intended use governs the specification far more than any general ranking of the three. None of the three replaces clinical judgement, and all are described here for research and assay-development use.

Selection for Assay Development

For a new assay, the decision is driven by the sample type, the required sensitivity and the dynamic range. IL-6 assays often need a broad working range and careful control of non-specific binding; PCT assays require attention to glycosylation and to the mature and precursor forms; hs-CRP demands high sensitivity because the reference range is low. Pepys and Hirschfield summarised the biology of CRP in the Journal of Clinical Investigation (2003), and Assicot and colleagues described PCT in sepsis in The Lancet (1993).

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