Inflammatory Markers Guide

A comprehensive reference for pediatricians and medical students

Acute Phase Proteins

C-Reactive Protein (CRP)

Type: Acute Phase Protein

Normal Range: < 10 mg/L

Function: Pattern recognition molecule that binds to phosphocholine on microorganisms and damaged cells, activating complement system.

Associated Conditions:

• Bacterial infections
• Rheumatic fever
• Inflammatory bowel disease
• Post-surgical inflammation
• Kawasaki disease

Clinical Significance: Rapid rise within 6-8 hours, peaks at 48 hours. More sensitive than ESR for acute inflammation.

Erythrocyte Sedimentation Rate (ESR)

Type: Non-specific Inflammatory Marker

Normal Range: 0-15 mm/hr (age and gender dependent)

Function: Measures rate of red blood cell sedimentation, influenced by plasma proteins, particularly fibrinogen.

Associated Conditions:

• Chronic inflammatory conditions
• Autoimmune diseases
• Malignancies
• Giant cell arteritis
• Rheumatoid arthritis

Clinical Significance: Changes more slowly than CRP, reflects disease activity in chronic conditions.

Procalcitonin (PCT)

Type: Acute Phase Protein

Normal Range: < 0.15 ng/mL

Function: Precursor of calcitonin, increases significantly in bacterial infections.

Associated Conditions:

• Severe bacterial infections
• Sepsis
• Bacterial meningitis
• Severe pneumonia

Clinical Significance: Highly specific for bacterial infections, helps guide antibiotic therapy.

Cytokines and Related Proteins

Interleukin-6 (IL-6)

Type: Pro-inflammatory Cytokine

Normal Range: < 7 pg/mL

Function: Key mediator of acute phase response, T-cell activation, and B-cell differentiation.

Associated Conditions:

• Systemic inflammatory response syndrome (SIRS)
• Cytokine release syndrome
• Severe COVID-19
• Still's disease
• Systemic juvenile idiopathic arthritis

Clinical Significance: Earlier marker than CRP, peaks within 4-6 hours of inflammatory stimulus.

Tumor Necrosis Factor-α (TNF-α)

Type: Pro-inflammatory Cytokine

Normal Range: < 10 pg/mL

Function: Mediates acute inflammation, regulates immune cells, induces apoptosis.

Associated Conditions:

• Rheumatoid arthritis
• Inflammatory bowel disease
• Psoriasis
• Septic shock

Clinical Significance: Target for biological therapies in autoimmune diseases.

Complement Proteins

C3 Complement

Type: Complement Protein

Normal Range: 88-252 mg/dL

Function: Central component of complement cascade, enhances phagocytosis and inflammation.

Associated Conditions:

• Systemic lupus erythematosus
• Post-streptococcal glomerulonephritis
• Membranoproliferative glomerulonephritis
• Bacterial infections

Clinical Significance: Low levels indicate complement consumption or decreased production.

C4 Complement

Type: Complement Protein

Normal Range: 12-72 mg/dL

Function: Component of classical complement pathway, involved in immune complex clearance.

Associated Conditions:

• Systemic lupus erythematosus
• Hereditary angioedema
• Immune complex diseases
• Cryoglobulinemia

Clinical Significance: Low levels may indicate genetic deficiency or consumption.

Interleukins (Comprehensive List)

Interleukin-1 (IL-1α and IL-1β)

Type: Pro-inflammatory Cytokine

Normal Range: < 5 pg/mL

Function: Initiates and amplifies inflammatory response, induces fever, activates acute phase proteins.

Associated Conditions:

• Autoinflammatory syndromes
• Familial Mediterranean Fever
• CAPS (Cryopyrin-Associated Periodic Syndromes)
• Systemic Juvenile Idiopathic Arthritis
• Acute infections

Clinical Significance: Target for biological therapy in autoinflammatory conditions.

Interleukin-2 (IL-2)

Type: T-cell Growth Factor

Normal Range: < 10 U/mL

Function: Promotes T-cell proliferation, supports Treg development, enhances NK cell activity.

Associated Conditions:

• Primary immunodeficiencies
• Cancer immunotherapy
• Autoimmune diseases
• IPEX syndrome

Clinical Significance: Used therapeutically in cancer treatment; marker of T-cell activation.

Interleukin-3 (IL-3)

Type: Hematopoietic Growth Factor

Normal Range: < 20 pg/mL

Function: Stimulates production of multiple blood cell lineages, supports mast cell growth.

Associated Conditions:

• Aplastic anemia
• Myelodysplastic syndromes
• Allergic inflammation
• Parasitic infections

Clinical Significance: Potential therapeutic target in bone marrow failure syndromes.

Interleukin-4 (IL-4)

Type: Th2 Cytokine

Normal Range: < 3 pg/mL

Function: Promotes Th2 differentiation, IgE class switching, allergic responses.

Associated Conditions:

• Allergic disorders
• Atopic dermatitis
• Asthma
• Parasitic infections
• STAT3 deficiency

Clinical Significance: Key marker in allergic diseases; therapeutic target in asthma.

Interleukin-5 (IL-5)

Type: Eosinophil Growth Factor

Normal Range: < 7.8 pg/mL

Function: Stimulates eosinophil production, activation, and survival.

Associated Conditions:

• Eosinophilic disorders
• Severe asthma
• Hypereosinophilic syndrome
• Allergic rhinitis
• EGPA (Eosinophilic Granulomatosis with Polyangiitis)

Clinical Significance: Target for biological therapy in severe eosinophilic asthma.

Interleukin-7 (IL-7)

Type: Lymphopoietic Growth Factor

Normal Range: 0.3-8.4 pg/mL

Function: Essential for T and B lymphocyte development, homeostatic proliferation.

Associated Conditions:

• Severe Combined Immunodeficiency (SCID)
• HIV infection
• Lymphopenia
• Post-transplant immune reconstitution

Clinical Significance: Potential therapeutic agent for immune reconstitution.

Interleukin-8 (IL-8/CXCL8)

Type: Chemokine

Normal Range: < 30 pg/mL

Function: Neutrophil chemotaxis and activation, angiogenesis promotion.

Associated Conditions:

• Acute respiratory distress syndrome (ARDS)
• Bronchiolitis
• Cystic fibrosis
• Sepsis
• Inflammatory lung diseases

Clinical Significance: Marker of neutrophilic inflammation and tissue damage.

Interleukin-9 (IL-9)

Type: T-cell Growth Factor

Normal Range: < 5 pg/mL

Function: Promotes mast cell and T-cell growth, enhances IgE production.

Associated Conditions:

• Asthma
• Allergic inflammation
• Parasitic infections
• Lymphoid malignancies

Clinical Significance: Emerging target in allergic disease therapy.

Interleukin-10 (IL-10)

Type: Anti-inflammatory Cytokine

Normal Range: < 20 pg/mL

Function: Suppresses inflammatory responses, inhibits pro-inflammatory cytokine production.

Associated Conditions:

• Inflammatory bowel disease
• Systemic lupus erythematosus
• Chronic infections
• IL-10 receptor deficiency
• Very Early Onset IBD

Clinical Significance: Important regulatory cytokine; potential therapeutic applications.

Interleukins (Continued)

Interleukin-11 (IL-11)

Type: Pleiotropic Cytokine

Normal Range: < 15 pg/mL

Function: Stimulates megakaryocytopoiesis, supports mucosal protection, promotes hematopoiesis.

Associated Conditions:

• Thrombocytopenia
• Inflammatory bowel disease
• Rheumatoid arthritis
• Chemotherapy-induced bone marrow suppression

Clinical Significance: Used therapeutically to treat thrombocytopenia.

Interleukin-12 (IL-12)

Type: Pro-inflammatory Cytokine

Normal Range: < 7.9 pg/mL

Function: Induces Th1 differentiation, stimulates IFN-γ production, enhances NK cell activity.

Associated Conditions:

• Mendelian Susceptibility to Mycobacterial Disease (MSMD)
• Chronic infections
• Autoimmune diseases
• IL-12 receptor deficiency
• Atypical mycobacterial infections

Clinical Significance: Key diagnostic marker in primary immunodeficiencies.

Interleukin-13 (IL-13)

Type: Th2 Cytokine

Normal Range: < 20 pg/mL

Function: Mediates allergic inflammation, stimulates mucus production, promotes fibrosis.

Associated Conditions:

• Asthma
• Atopic dermatitis
• Allergic rhinitis
• Pulmonary fibrosis
• Eosinophilic esophagitis

Clinical Significance: Therapeutic target in severe asthma and atopic conditions.

Interleukin-15 (IL-15)

Type: Pro-inflammatory Cytokine

Normal Range: < 3.5 pg/mL

Function: Promotes NK cell development and survival, supports memory T-cell homeostasis.

Associated Conditions:

• Celiac disease
• NK cell deficiencies
• Refractory celiac disease
• Inflammatory myopathies

Clinical Significance: Potential therapeutic target in cancer immunotherapy.

Interleukin-17 (IL-17A and IL-17F)

Type: Pro-inflammatory Cytokine

Normal Range: < 15 pg/mL

Function: Mediates neutrophil recruitment, induces antimicrobial peptides, promotes inflammation.

Associated Conditions:

• Chronic mucocutaneous candidiasis
• Psoriasis
• IL-17 receptor deficiency
• STAT3 deficiency
• Inflammatory bowel disease

Clinical Significance: Target for biological therapy in psoriasis and other autoimmune conditions.

Interleukin-18 (IL-18)

Type: Pro-inflammatory Cytokine

Normal Range: 36-257 pg/mL

Function: Induces IFN-γ production, activates NK cells, promotes Th1 responses.

Associated Conditions:

• Macrophage Activation Syndrome
• Systemic Juvenile Idiopathic Arthritis
• Adult-onset Still's disease
• NLRC4-associated autoinflammatory diseases

Clinical Significance: Biomarker for macrophage activation syndrome.

Interleukin-21 (IL-21)

Type: Pleiotropic Cytokine

Normal Range: < 30 pg/mL

Function: Regulates B, T, and NK cell responses, promotes plasma cell differentiation.

Associated Conditions:

• Common Variable Immunodeficiency
• IL-21 receptor deficiency
• Autoimmune diseases
• Primary immunodeficiencies

Clinical Significance: Important in antibody responses and immunodeficiency diagnosis.

Interleukin-22 (IL-22)

Type: Tissue-Protective Cytokine

Normal Range: < 10 pg/mL

Function: Promotes epithelial barrier function, tissue repair, and antimicrobial defense.

Associated Conditions:

• Inflammatory bowel disease
• Psoriasis
• Atopic dermatitis
• Graft-versus-host disease

Clinical Significance: Potential therapeutic target in tissue repair and mucosal immunity.

Interleukins (Final Set)

Interleukin-23 (IL-23)

Type: Pro-inflammatory Cytokine

Normal Range: < 16 pg/mL

Function: Promotes Th17 cell development, maintains inflammatory responses.

Associated Conditions:

• Psoriasis
• Inflammatory bowel disease
• Ankylosing spondylitis
• IL-23R deficiency
• Psoriatic arthritis

Clinical Significance: Target for biological therapy in psoriasis and IBD.

Interleukin-27 (IL-27)

Type: Immunoregulatory Cytokine

Normal Range: < 25 pg/mL

Function: Regulates T cell responses, suppresses inflammation, inhibits Th17 development.

Associated Conditions:

• Autoimmune diseases
• Chronic infections
• Cancer
• Primary immunodeficiencies

Clinical Significance: Potential therapeutic agent for autoimmune diseases.

Interleukin-33 (IL-33)

Type: Alarmin Cytokine

Normal Range: < 1 ng/mL

Function: Alarm signal upon cell damage, activates type 2 immune responses.

Associated Conditions:

• Asthma
• Atopic dermatitis
• Food allergies
• Inflammatory bowel disease
• COPD

Clinical Significance: Emerging target in allergic disease therapy.

Interleukin-35 (IL-35)

Type: Immunosuppressive Cytokine

Normal Range: < 70 pg/mL

Function: Suppresses inflammatory responses, promotes regulatory T cell function.

Associated Conditions:

• Autoimmune diseases
• Chronic infections
• Cancer
• Transplant rejection

Clinical Significance: Potential therapeutic agent in autoimmune conditions.

Acute Phase Proteins

Ferritin

Type: Acute Phase Protein

Normal Range: 12-300 ng/mL (age/gender dependent)

Function: Iron storage protein, increases during inflammation.

Associated Conditions:

• Hemophagocytic lymphohistiocytosis (HLH)
• Still's disease
• Macrophage activation syndrome
• Chronic inflammatory conditions

Clinical Significance: Key diagnostic marker for HLH and MAS.

Serum Amyloid A (SAA)

Type: Acute Phase Protein

Normal Range: < 10 mg/L

Function: HDL-associated protein, increases dramatically during inflammation.

Associated Conditions:

• Familial Mediterranean Fever
• AA amyloidosis
• Periodic fever syndromes
• Chronic inflammatory conditions

Clinical Significance: Predictor of risk for AA amyloidosis.

Cellular Markers of Inflammation

CD64 Expression on Neutrophils

Type: Cell Surface Marker

Normal Range: < 2000 molecules/cell

Function: High-affinity Fc receptor, upregulated during bacterial infections.

Associated Conditions:

• Bacterial sepsis
• Systemic inflammation
• Neonatal infections
• Autoimmune diseases

Clinical Significance: Early marker of bacterial infection.

HLA-DR Expression on Monocytes

Type: Cell Surface Marker

Normal Range: > 30,000 molecules/cell

Function: Antigen presentation molecule, decreases in immunoparalysis.

Associated Conditions:

• Sepsis
• Severe trauma
• Major surgery
• Immunosuppression

Clinical Significance: Marker of immune function in critical illness.

Specialized Inflammatory Markers

Calprotectin

Type: Neutrophil Protein

Normal Range: < 50 μg/g (fecal)

Function: Antimicrobial protein, marker of neutrophil activation.

Associated Conditions:

• Inflammatory bowel disease
• Infectious enteritis
• Juvenile idiopathic arthritis
• Intestinal inflammation

Clinical Significance: Non-invasive marker of intestinal inflammation.

Neopterin

Type: Macrophage Activation Marker

Normal Range: < 2.5 ng/mL

Function: Product of activated macrophages, reflects cellular immune activation.

Associated Conditions:

• Viral infections
• Autoimmune diseases
• Cancer
• Allograft rejection

Clinical Significance: Marker of cell-mediated immune activation.

Advanced Specialized Inflammatory Markers

Myeloperoxidase (MPO)

Type: Neutrophil Enzyme

Normal Range: < 0.4 U/mL

Function: Produces hypochlorous acid for bacterial killing, marker of neutrophil activation.

Associated Conditions:

• ANCA-associated vasculitis
• Microscopic polyangiitis
• Acute coronary syndromes
• MPO deficiency
• Neutrophilic inflammation

Clinical Significance: Diagnostic marker for MPO-ANCA vasculitis and monitoring disease activity.

Beta-2 Microglobulin (β2M)

Type: MHC Class I Protein

Normal Range: 0.7-1.8 mg/L

Function: Component of MHC class I molecules, marker of immune activation.

Associated Conditions:

• Lymphoproliferative disorders
• HIV infection
• Autoimmune diseases
• Kidney disease
• Multiple myeloma

Clinical Significance: Prognostic marker in lymphoid malignancies and HIV.

Matrix Metalloproteinase-9 (MMP-9)

Type: Tissue Remodeling Enzyme

Normal Range: 169-705 ng/mL

Function: Degrades extracellular matrix, involved in tissue remodeling and inflammation.

Associated Conditions:

• Asthma
• Bronchiectasis
• Pulmonary fibrosis
• Inflammatory arthritis
• Cancer metastasis

Clinical Significance: Marker of tissue destruction and remodeling.

YKL-40 (Chitinase-3-like protein 1)

Type: Glycoprotein

Normal Range: 20-100 ng/mL

Function: Involved in tissue remodeling and inflammation, produced by macrophages.

Associated Conditions:

• Severe asthma
• Liver fibrosis
• Rheumatoid arthritis
• Cancer progression
• Inflammatory bowel disease

Clinical Significance: Biomarker of disease severity in chronic inflammatory conditions.

Lipocalin-2 (NGAL)

Type: Acute Phase Protein

Normal Range: < 20 ng/mL

Function: Iron sequestration, antimicrobial defense, kidney injury marker.

Associated Conditions:

• Acute kidney injury
• Systemic infections
• Inflammatory bowel disease
• Neutrophilic inflammation
• Sepsis

Clinical Significance: Early marker of kidney injury and inflammation.

Pentraxin-3 (PTX3)

Type: Pattern Recognition Molecule

Normal Range: < 2 ng/mL

Function: Component of innate immunity, complement activation.

Associated Conditions:

• Vascular inflammation
• Acute coronary syndromes
• Sepsis
• Small vessel vasculitis
• Severe infections

Clinical Significance: Marker of vascular inflammation and tissue damage.

Soluble CD163 (sCD163)

Type: Macrophage Activation Marker

Normal Range: 0.7-3.9 mg/L

Function: Hemoglobin scavenger receptor, marker of macrophage activation.

Associated Conditions:

• Hemophagocytic lymphohistiocytosis
• Macrophage activation syndrome
• Liver disease
• Systemic sclerosis
• Sepsis

Clinical Significance: Biomarker of macrophage activation and inflammation.

S100 Proteins (S100A8/A9, S100A12)

Type: Damage-Associated Molecular Patterns

Normal Range: < 2.9 μg/mL (S100A8/A9)

Function: Calcium-binding proteins, alarmins released during tissue damage.

Associated Conditions:

• Juvenile idiopathic arthritis
• Systemic-onset JIA
• Inflammatory bowel disease
• Periodic fever syndromes
• Kawasaki disease

Clinical Significance: Biomarkers of neutrophil-mediated inflammation.