Inflammatory Markers
Inflammatory markers are blood tests that help identify inflammation within the body. They are commonly requested when infection, autoimmune disease, tissue injury or other inflammatory conditions are suspected. Although these tests can indicate that inflammation is present, they do not identify the underlying cause. Results should always be interpreted alongside the patient's history, clinical presentation and other investigations.
What You Need to Know
Inflammation is a normal physiological response that occurs when the body detects infection, injury or tissue damage. As part of this response, immune cells release chemical mediators (cytokines), such as interleukin-1 (IL-1) and interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), which help destroy harmful organisms, remove damaged tissue and promote healing. These cytokines also stimulate the production of acute phase proteins, such as C-reactive protein (CRP), that can be measured in the blood.
Several blood tests are used to assess inflammation, each providing different information. Some markers rise rapidly during acute inflammation, while others increase more slowly or remain elevated for longer periods. No single inflammatory marker is specific for infection, and normal results do not always exclude serious illness.
Inflammatory markers are often used to:
Support the diagnosis of infection or inflammatory disease.
Assess the severity of illness.
Monitor response to treatment.
Identify trends over time.
Assist with clinical decision-making alongside other investigations.
Inflammatory markers should rarely be interpreted in isolation. A patient with a markedly elevated C-reactive protein (CRP) may have pneumonia, pancreatitis, major trauma or an autoimmune flare. Likewise, a patient with severe sepsis may initially have only mildly elevated inflammatory markers, particularly early in the disease process.
White blood cells (leukocytes) are a key component of the body's immune system and play an important role in the inflammatory response. When infection, tissue injury or inflammation occurs, cytokines stimulate the bone marrow to produce and release additional white blood cells into the bloodstream. These cells travel to the affected area where they help identify and destroy pathogens, remove damaged tissue and coordinate the immune response. As a result, the white blood cell count often increases during inflammation.
The type of white blood cell that increases can also provide important diagnostic clues. For example, neutrophils commonly increase during bacterial infections, whereas lymphocytes are more often associated with viral infections. However, these patterns are not diagnostic and should always be interpreted alongside the patient's clinical presentation and other investigations.
Key points
Inflammatory markers indicate that inflammation is occurring somewhere in the body.
They do not identify the cause of inflammation.
Infection is only one cause of elevated inflammatory markers.
Trends are often more useful than a single result.
Results should always be interpreted alongside the patient's clinical presentation and other investigations.
Components of Inflammatory Markers:
C-reactive protein (CRP)
Erythrocyte sedimentation rate (ESR)
Procalcitonin (PCT)
White blood cells (WBC)
Clinical pearl: Ferritin is both an iron-storage protein and an acute-phase reactant (the concentration changes in reaction to inflammation). During inflammation, infection or tissue injury, ferritin levels may increase even when iron stores are low, potentially masking underlying iron deficiency.
Beyond the Basics
C-Reactive Protein (CRP)
Reference range
Less than 5 mg/L (may vary slightly between laboratories)
C-reactive protein (CRP) is produced by the liver in response to inflammatory cytokines, particularly interleukin-6 (IL-6), released during infection, tissue injury or inflammation. As part of the body's acute inflammatory response, CRP helps the immune system recognise and remove damaged cells and pathogens. CRP begins to rise within approximately 6–8 hours of an inflammatory stimulus, usually peaks within 48 hours and falls relatively quickly once the inflammation resolves.
Because CRP responds rapidly to changes in inflammation, it is commonly used to monitor disease progression and response to treatment.
Elevated CRP
An elevated CRP may occur with:
Bacterial infections
Viral infections
Autoimmune diseases
Trauma
Surgery
Burns
Pancreatitis
Myocardial infarction
Malignancy
Higher CRP levels are often associated with more significant inflammation, although there is considerable overlap between different conditions. A markedly elevated CRP should prompt further assessment but does not identify the underlying diagnosis.
Decreased CRP
Low CRP levels are generally considered normal and are not clinically significant.
CRP is best interpreted as a trend. For example, a patient whose CRP falls from 240 mg/L to 90 mg/L after commencing antibiotics is usually improving, even though the result remains significantly elevated.
Erythrocyte Sedimentation Rate (ESR)
Reference range
Male: Less than 15 mm/hour
Female: Less than 20 mm/hour
(Reference ranges vary with age.)
The erythrocyte sedimentation rate (ESR) measures how quickly red blood cells settle to the bottom of a test tube over one hour. During inflammation, proteins released into the bloodstream cause red blood cells to clump together and settle more rapidly, resulting in an increased ESR.
Unlike CRP, ESR rises and falls more slowly. It may remain elevated for weeks after inflammation has resolved. An elevated ESR indicates that inflammation has been present long enough to increase proteins such as fibrinogen, which cause red blood cells to settle more quickly. However, it does not indicate when the inflammation started or whether it is acute or chronic.
This is why clinicians often use CRP and ESR together:
CRP is better at detecting acute changes and monitoring response to treatment.
ESR is better at assessing ongoing inflammatory activity in chronic conditions.
Elevated ESR
An elevated ESR may occur with:
Autoimmune diseases
Chronic infections
Osteomyelitis
Temporal arteritis
Polymyalgia rheumatica
Malignancy
Chronic kidney disease
Pregnancy
ESR is particularly useful when investigating chronic inflammatory conditions because ongoing inflammation causes it to remain persistently elevated, making it a useful marker of long-term inflammatory activity.
Decreased ESR
A reduced ESR is uncommon and is generally of little clinical significance. It may occur in conditions such as polycythaemia or sickle cell disease. Because ESR changes slowly, it is less useful than CRP for monitoring rapid clinical improvement or deterioration.
Procalcitonin (PCT)
Reference range
Less than 0.1 ng/mL (reference ranges vary between laboratories)
Procalcitonin is a protein precursor of calcitonin (a hormone produced by the thyroid gland that helps to regulate blood calcium and phosphate levels) that increases primarily during bacterial infections. Procalcitonin is normally produced in very small amounts by the thyroid.
During systemic bacterial infections, bacterial toxins and inflammatory cytokines stimulate tissues throughout the body to produce procalcitonin, causing blood levels to rise. Although the exact purpose of this response is not fully understood, viral infections suppress procalcitonin production, making it a more useful marker of bacterial infection than many other inflammatory markers.
Procalcitonin is increasingly used in emergency departments and intensive care units to assist with antibiotic stewardship and the assessment of suspected sepsis.
Elevated procalcitonin
An elevated procalcitonin may occur with:
Bacterial sepsis
Severe bacterial pneumonia
Meningitis
Pyelonephritis
Severe bacterial infections
Levels may also increase following:
Major trauma
Major surgery
Severe burns
Cardiogenic shock
Low procalcitonin
Low procalcitonin levels make significant bacterial infection less likely, although they do not completely exclude it.
Procalcitonin should never be used alone to decide whether antibiotics are required. It should always be interpreted alongside the patient's clinical presentation, examination findings and other investigations.
White Blood Cell Count (WBC)
Reference range
4.0–11.0 × 10⁹/L (may vary slightly between laboratories)
The white blood cell count (WBC) measures the total number of white blood cells circulating in the bloodstream. White blood cells play a vital role in the body's immune response by recognising pathogens, coordinating inflammation and helping repair damaged tissue. Because of this, changes in the WBC often provide an early indication that the body is responding to infection, inflammation or physiological stress.
Elevated WBC: An elevated WBC (leukocytosis) most commonly occurs in response to bacterial infections and inflammatory conditions. It may also increase following trauma, surgery, burns, corticosteroid therapy, physical or emotional stress, and in some haematological disorders such as leukaemia. Although an elevated WBC suggests the body is mounting an immune response, it does not identify the underlying cause and should always be interpreted alongside the patient's clinical presentation and other investigations.
Low WBC: A reduced WBC (leukopenia) may occur with viral infections, bone marrow suppression, chemotherapy, autoimmune disorders and some severe bacterial infections, including overwhelming sepsis. A normal or low WBC does not exclude serious infection, particularly in older adults, immunocompromised patients or those presenting early in the disease process.
The total WBC provides only part of the picture. The differential white cell count, particularly neutrophils and lymphocytes, often provides additional information about the underlying cause and should be interpreted alongside the total WBC.
In Practice
Understanding what inflammatory markers measure is only the first step. In clinical practice, these tests are interpreted alongside the patient's history, observations, physical examination and other investigations.
Scenario 1: Community-acquired pneumonia
A 63-year-old man presents with a four-day history of fever, productive cough and increasing shortness of breath. He reports coughing up purulent sputum and feeling increasingly lethargic. He is febrile (38.8°C) and tachypnoeic (RR 28 breaths/min). A chest X-ray demonstrates consolidation in the right middle and lower lobes, consistent with pneumonia.
Inflammatory markers:
CRP: 186 mg/L
ESR: 48 mm/hour
Procalcitonin: 3.6 ng/mL
WBC: 16.8 × 10⁹/L
Interpretation: All inflammatory markers are elevated. The raised white blood cell count, markedly elevated CRP and procalcitonin support the presence of a significant bacterial infection. Combined with the patient's symptoms and chest X-ray findings, these results are consistent with bacterial pneumonia.
Scenario 2: Rheumatoid arthritis flare
A 52-year-old woman with a history of rheumatoid arthritis presents with worsening pain, swelling and stiffness affecting both hands and wrists. She reports that her morning stiffness now lasts more than two hours and she is finding it increasingly difficult to complete everyday tasks, such as dressing and preparing meals. She denies fever or other symptoms of infection.
Inflammatory markers:
CRP: 42 mg/L
ESR: 68 mm/hour
Procalcitonin: <0.05 ng/mL
WBC: 8.6 × 10⁹/L
Interpretation: The elevated CRP and ESR indicate active inflammation. The normal white blood cell count and procalcitonin make a significant bacterial infection less likely. In the context of her medical history, these findings are most consistent with an autoimmune flare.
Scenario 3: Post-operative recovery
A 70-year-old man is reviewed three days after a total hip replacement. He has no clinical features to suggest infection, such as fever, wound erythema or purulent discharge.
Inflammatory markers:
CRP: 128 mg/L
ESR: 32 mm/hour
Procalcitonin: <0.05 ng/mL
WBC: 8.9 × 10⁹/L
Interpretation: Inflammatory markers commonly rise following major surgery due to tissue injury. In the absence of fever, wound complications or clinical deterioration, these results may represent a normal post-operative inflammatory response. Ongoing monitoring and clinical assessment remain essential.
Scenario 4: Suspected sepsis
A 78-year-old woman presents to the emergency department with increasing confusion, fever and reduced oral intake over the past two days. Her family report she has become progressively drowsy and less responsive since that morning. On assessment, she is hypotensive, tachycardic and febrile. Urinalysis is positive for nitrites and leukocytes, and a urinary tract infection is suspected.
Inflammatory markers:
CRP: 265 mg/L
ESR: 60 mm/hour
Procalcitonin: 12.8 ng/mL
WBC: 21.4 × 10⁹/L
Interpretation: The markedly elevated white blood cell count, CRP and procalcitonin support a severe bacterial infection. Together with the patient's clinical presentation, these findings are highly suggestive of sepsis. Prompt antimicrobial therapy and resuscitation should not be delayed while awaiting further investigations.
Scenario 5: Viral illness
A 24-year-old woman presents to the emergency department with a two-day history of fever, sore throat, generalised muscle aches and fatigue. She reports several family members have recently experienced similar symptoms. On assessment, she is alert, haemodynamically stable and has no clinical features to suggest a bacterial infection.
Inflammatory markers
CRP: 24 mg/L
ESR: 18 mm/hour
Procalcitonin: <0.05 ng/mL
WBC: 6.2 × 10⁹/L
Interpretation: The normal white blood cell count, mildly elevated CRP and low procalcitonin make a significant bacterial infection less likely. Combined with the clinical presentation, these findings are most consistent with a viral illness. Clinical assessment remains the most important factor when determining management.