From the Guidelines
Elevated Interleukin-18 (IL-18) levels are a significant indicator of ongoing inflammation and potential macrophage activation syndrome (MAS), particularly in the context of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease, as evidenced by studies such as 1 and 1. The clinical significance of an elevated IL-18 level can be understood by its role as a pro-inflammatory cytokine involved in the pathogenesis of various inflammatory and autoimmune conditions.
Key Points to Consider:
- Elevated IL-18 levels have been associated with a predisposition to the development of MAS in the sJIA population, with high sensitivity and specificity, as shown in studies like 1.
- The measurement of total IL-18 is routine and clinically graded tests are becoming available, making it a practical biomarker for diagnostic purposes.
- IL-18 elevation is not diagnostic of any specific condition but serves as a marker of immune system activation, necessitating a comprehensive clinical assessment to determine the underlying cause.
- Other biomarkers such as CXCL9, S100A12, and ADA2 activity have also been identified as potential diagnostic markers for MAS, often in conjunction with IL-18 levels, as discussed in 1 and 1.
Recommendations:
- A thorough medical history, physical examination, and additional laboratory tests (e.g., complete blood count, C-reactive protein) should be conducted to understand the context of the IL-18 elevation.
- Symptoms such as joint pain, fever, or fatigue accompanying an elevated IL-18 level should be immediately reported to a healthcare provider for appropriate management.
- Consideration of alternative diagnoses, including malignancies, infectious diseases, and other immune-mediated inflammatory diseases, is crucial, as outlined in 1. Given the potential implications of elevated IL-18 levels on morbidity, mortality, and quality of life, particularly in the context of MAS and related conditions, prompt and thorough clinical evaluation and management are essential.
From the Research
Significance of Elevated Interleukin-18 (IL-18) Levels
Elevated IL-18 levels have been reported in various immune-related diseases, including:
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Type I diabetes mellitus
- Atopic dermatitis
- Psoriasis
- Inflammatory bowel disease 2
- Chronic obstructive pulmonary disease
- Crohn's disease 3
- Adult-onset Still's disease 4
Role of IL-18 in Disease Pathogenesis
IL-18 is a potent pro-inflammatory cytokine involved in host defense against infections and regulates the innate and acquired immune response 2. It plays a significant role in the pathogenesis of various diseases, including:
- Hemophagocytic syndromes (HS) also termed Macrophage Activation Syndrome 3
- Systemic juvenile idiopathic arthritis 3
- Inflammatory and cytotoxic immune cell activities leading to autoimmunity 2
Therapeutic Potential of Targeting IL-18
IL-18 has been identified as a potential therapeutic target in chronic autoimmune/inflammatory conditions 5. Blocking IL-18 function has been shown to prevent or ameliorate disease processes in animal models 5. However, the effectiveness of IL-18 blockade in human studies has been limited, and combination drug therapies targeting IL-18 and other cytokines may be necessary to achieve significant therapeutic benefits 2, 6