From the Guidelines
Elevated Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18) levels have been associated with various bodily effects, including:
- Inflammation: IL-1β and IL-18 are pro-inflammatory cytokines that play a crucial role in the inflammatory response, leading to increased production of other inflammatory mediators and activation of immune cells 1.
- Fever: Elevated IL-18 levels have been linked to the development of fever, a common symptom of various inflammatory and infectious diseases 1.
- Macrophage activation syndrome (MAS): IL-18 has been identified as a key player in the pathogenesis of MAS, a life-threatening condition characterized by excessive activation of macrophages and T cells 1.
- Autoinflammatory diseases: IL-1β and IL-18 have been implicated in the pathogenesis of various autoinflammatory diseases, including systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) 1.
- Immune system activation: IL-1β and IL-18 can activate various immune cells, including T cells, macrophages, and natural killer cells, leading to the production of other cytokines and chemokines that amplify the immune response 1.
Some key biomarkers associated with elevated IL-1β and IL-18 levels include:
- S100 proteins: S100A8, S100A9, and S100A12 have been identified as potential biomarkers for Still's disease and MAS 1.
- Ferritin: Elevated ferritin levels have been linked to various inflammatory and autoimmune diseases, including sJIA and AOSD 1.
- CXCL9: This chemokine has been identified as a potential biomarker for MAS, with elevated levels observed in patients with sJIA-MAS 1.
Overall, elevated IL-1β and IL-18 levels can have significant effects on the body, leading to inflammation, immune system activation, and various disease manifestations.
From the Research
Bodily Effects of Elevated IL-1β and IL-18 Levels
The bodily effects of elevated Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18) levels are multifaceted and can have both beneficial and detrimental consequences. Some of the key effects include:
- Promotion of tumor growth and metastasis through the expression of IL-1 targets that promote neoangiogenesis and the production of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells 2
- Induction of inflammatory responses, including the activation of innate immune cells, such as antigen-presenting cells, and the polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells 2
- Participation in fundamental inflammatory processes that increase during the aging process, including the development of atherosclerosis 3
- Unique signaling pathways, with IL-18 inducing IFN-gamma from T lymphocytes and natural killer cells, but not causing fever, whereas IL-1β induces fever and activates the NF-kappaB pathway 4
- Suppression of anti-tumor immune responses and promotion of tumor angiogenesis due to its effects on the differentiation of epithelial cells, pro-angiogenic molecule secretion, and expression of adhesion molecules 5
Disease Associations
Elevated IL-1β and IL-18 levels have been associated with various diseases, including:
- Cancer, with IL-1β exhibiting pro-oncogenic properties and IL-18 playing a role in the pathogenesis of hemophagocytic syndromes (HS) 2, 6
- Infectious diseases, such as influenza virus infection, and metabolic or inflammatory diseases, such as atheroma, myocardial infarction, chronic obstructive pulmonary disease, or Crohn's disease 6
- Systemic juvenile idiopathic arthritis or adult-onset Still's disease, characterized by high serum IL-18 concentrations 6
- Atherosclerosis, with IL-1β and IL-18 participating in the pathogenesis of the disease 3
Therapeutic Implications
The use of IL-1β and IL-18 inhibitors has been explored as a potential therapeutic strategy for the treatment of various diseases, including:
- Cancer, with IL-1β inhibitors contributing to a decrease in tumor mass and an increase in the response to anti-tumour drugs 5
- Hemophagocytic syndromes (HS), with IL-18BP used as a specific treatment 6
- Autoimmune diseases, with agents for pharmacological inhibition of IL-1 signaling used therapeutically 2