Clinical laboratory differentiation of infectious versus non-infectious systemic inflammatory response syndrome

Clin Chim Acta. 2005 Jan;351(1-2):17-29. doi: 10.1016/j.cccn.2004.08.018.


Objective: To evaluate the accuracy of C-reactive protein (CRP), procalcitonin (PCT), neopterin, and endotoxin in the differential diagnosis of sepsis and non-infectious systemic inflammatory response syndrome (SIRS).

Methods: A Medline database and references from identified articles were used to perform a literature search relating to the differential diagnosis of sepsis versus non-infectious SIRS.

Results: CRP, PCT, and neopterin are released both in sepsis and in non-infectious inflammatory disease. CRP and PCT are equally effective, although not perfect, in differentiating between sepsis and non-infectious SIRS. However, CRP and PCT have different kinetics and profiles. The kinetics of CRP is slower than that of PCT, and CRP levels may not further increase during more severe stages of sepsis. On the contrary, PCT rises in proportion to the severity of sepsis and reaches its highest levels in septic shock. PCT tends to be higher in nonsurvivor than in survivor. Therefore, PCT demonstrated a closer correlation with the severity of sepsis and outcome than CRP. Unlike CRP and PCT, neopterin is increased in viral infection as well as bacterial infection, and neopterin is also a useful indicator of sepsis. Endotoxemia was detected in no more than half of patients with Gram-negative bacteremia, and Gram-negative bacteremia was detected in half of patients with endotoxemia.

Conclusions: The diagnostic capacity of PCT is superior to that of CRP due to the close correlation between PCT levels and the severity of sepsis and outcome. Neopterin is very useful in the diagnosis of viral infection. The endotoxin assay in combination with CRP, PCT, or neopterin may help as a diagnostic marker for Gram-negative bacterial infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers
  • C-Reactive Protein / analysis
  • Calcitonin / analysis
  • Calcitonin Gene-Related Peptide
  • Diagnosis, Differential
  • Humans
  • Infections / complications*
  • Infections / diagnosis*
  • Neopterin / blood
  • Protein Precursors / analysis
  • Systemic Inflammatory Response Syndrome / diagnosis*
  • Systemic Inflammatory Response Syndrome / etiology*


  • Biomarkers
  • CALCA protein, human
  • Protein Precursors
  • Neopterin
  • Calcitonin
  • C-Reactive Protein
  • Calcitonin Gene-Related Peptide