From the Guidelines
Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18) play crucial roles in inflammation, with IL-1β being a key pro-inflammatory cytokine and IL-18 promoting inflammatory responses, particularly in autoinflammatory disorders.
Key Roles of IL-1β and IL-18
- IL-1β is involved in the regulation of immune responses and the promotion of inflammation, making it a target for therapies in conditions like systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) 1.
- IL-18 has been identified as a significant biomarker in sJIA and AOSD, with elevated levels indicating disease activity and potential complications such as macrophage activation syndrome (MAS) 1.
Involvement in Autoinflammatory Disorders
Both IL-1β and IL-18 are implicated in the pathogenesis of autoinflammatory disorders, which are characterized by an excessive inflammatory response due to dysregulation of the innate immune system 1.
Diagnostic and Therapeutic Implications
- Elevated levels of IL-18 can aid in the diagnosis of sJIA and AOSD, distinguishing these conditions from other inflammatory and infectious diseases 1.
- Targeting the IL-1 pathway has been a successful therapeutic strategy in managing sJIA and AOSD, highlighting the importance of IL-1β in the inflammatory process 1.
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The understanding of IL-1β and IL-18's roles in inflammation and autoinflammatory disorders continues to evolve, with ongoing research aimed at improving diagnostic accuracy and therapeutic outcomes for patients with sJIA and AOSD 1.
From the Research
Roles of IL-1β and IL-18 in Inflammation
- IL-1β and IL-18 are cytokines that play a major role in autoimmune and inflammatory human disease, driving pro-inflammatory effector networks in many cell types 2.
- Both cytokines are expressed at elevated levels in tissue and fluid samples isolated from patients with many chronic inflammatory diseases, and their blockade has been shown to ameliorate disease in preclinical studies 2.
- IL-18 is involved in Th1 and NK cell activation, but also in Th2, IL-17-producing γδ T cells and macrophage activation, and uses the same signaling pathway as IL-1 to activate NF-kB and induce inflammatory mediators 3.
Mechanisms of Action
- IL-18 binds to its specific receptor (IL-18Rα) forming a low affinity ligand chain, followed by recruitment of the IL-18Rβ chain, and then uses the same signaling pathway as IL-1 to activate NF-kB and induce inflammatory mediators 3.
- IL-1β is only induced in response to inflammatory stimuli, but IL-18 is constitutively expressed, and type I IFN signaling is essential for induction of IL-18 4.
- IL-1β and IL-18 are released from cells through the formation and activation of multiprotein complexes, termed inflammasomes, and each lead to different downstream consequences 5.
Disease Associations
- IL-18 plays a very specific role in the pathogenesis of hemophagocytic syndromes (HS) also termed Macrophage Activation Syndrome, and is treated with the IL-1 Receptor antagonist (anakinra) or IL-18BP 3.
- Systemic juvenile idiopathic arthritis or adult-onset Still's disease are also characterized by high serum IL-18 concentrations and are treated by IL-18BP 3.
- IL-1β and IL-18 are important proinflammatory cytokines that activate monocytes, macropages, and neutrophils, and induce Th1 and Th17 adaptive cellular responses, and are involved in various infectious, metabolic or inflammatory diseases 6.