What are the best inflammatory markers?

Best Inflammatory Markers for Clinical Practice

C-reactive protein (CRP) is the single best inflammatory marker for routine clinical use, having superior analyte and assay characteristics compared to all other available inflammatory markers. 1

Why CRP is Superior

The CDC/AHA guidelines definitively establish CRP as the optimal inflammatory marker based on comprehensive laboratory evaluation 1:

• Assay standardization: CRP has proficiency testing programs through the College of American Pathologists and standardization programs at the CDC, unlike other markers 1
• Analyte stability: CRP remains stable in serum/plasma without requiring immediate processing or freezing to -70°C (unlike cytokines) 1
• Commercial availability: Widely available high-sensitivity CRP (hs-CRP) assays with acceptable precision down to 0.3 mg/L 1
• Acceptable precision: Coefficient of variation is consistently acceptable across platforms 1

Practical CRP Measurement Protocol

When ordering CRP for inflammatory assessment 1:

• Obtain 2 measurements (fasting or nonfasting) optimally 2 weeks apart and average the results
• If CRP >10 mg/L: Repeat the test and evaluate for acute infection or inflammation
• Report results in mg/L to 1 decimal point only

Risk Stratification Using CRP

Use these specific cutoffs for cardiovascular and inflammatory risk assessment 1:

• Low risk: <1.0 mg/L
• Average risk: 1.0-3.0 mg/L
• High risk: >3.0 mg/L

Other Inflammatory Markers: Why They Are Inferior

Erythrocyte Sedimentation Rate (ESR)

• Limited utility: Longer half-life makes it better for chronic conditions but less useful for acute assessment 2
• Better for monitoring: More appropriate for tracking chronic inflammatory diseases rather than diagnosis 2, 3
• Use alongside CRP: ESR and CRP together provide complementary information, with CRP superior for acute conditions 1, 4

Cytokines (IL-6, TNF-α, IL-1, IL-8, IL-10, IL-18)

• Research tools only: Require immediate processing and freezing to -70°C 1
• Short half-life: Some cytokines like IL-1 degrade rapidly 1
• Standardization problems: Different antibody pairs prevent comparable results between assays 1
• Cannot quantify normal ranges: Most assays designed for acute inflammation cannot measure low concentrations in healthy individuals 1

Soluble Adhesion Molecules (sICAM-1, sVCAM-1, E-selectin, P-selectin)

• Not ready for clinical use: Precluded from routine laboratory use for same reasons as cytokines 1

Fibrinogen

• Stability issues: Unstable unless analyzed immediately with clotting assays 1
• Standardization problems: WHO standard exists only for mass assays, not the commonly used functional assays 1
• Variable methodology: Different measurement methods (immunoassay vs. functional) complicate interpretation 1

Serum Amyloid A (SAA)

• Limited clinical validation: Less extensively studied than CRP for clinical decision-making 1
• No clear advantage: Does not outperform CRP in predictive ability 1

Clinical Context: When to Use Which Marker

For acute inflammatory assessment in emergency settings 1:

• CRP is mandatory
• ESR provides complementary information
• Full blood count with differential
• Fecal calprotectin when inflammatory bowel disease is suspected

For chronic inflammatory monitoring 2, 3:

• ESR may be more appropriate due to longer half-life
• CRP for assessing treatment response

Important Caveats

CRP elevation occurs in multiple conditions beyond infection 1:

• Inflammatory bowel disease
• Rheumatoid arthritis
• Long-term alcoholism
• Any acute inflammatory process

Neither ESR nor CRP are specific 3, 5:

• Must be interpreted with clinical history and physical examination
• Not all systemic rheumatic diseases show elevation 5
• Discordance between ESR and CRP is common in chronic inflammatory conditions 3

IL-6 and CRP have non-inflammatory roles 6:

• Both participate in somatic maintenance beyond inflammation
• Elevated levels may reflect tissue repair or pathogen tolerance, not just inflammation