From the Guidelines
Elevated levels of Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18) are indicative of NLRP3 (Nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3) activation.
Key Findings
- The activation of the NLRP3 inflammasome leads to the cleavage of pro-IL-1β and pro-IL-18, resulting in the production of mature IL-1β and IL-18 1.
- Elevated levels of IL-1β and IL-18 have been observed in various conditions, including ischemic stroke and macrophage activation syndrome (MAS), which are associated with NLRP3 activation 1.
- The NLRP3 inflammasome can be activated by various stimuli, including mitochondrial dysfunction, oxidative stress, and the release of mitochondrial DNA (mtDNA) into the cytosol 1.
NLRP3 Activation Mechanism
- The NLRP3 inflammasome is a multiprotein complex that plays a crucial role in the innate immune response 1.
- The activation of NLRP3 leads to the recruitment of caspase-1, which cleaves pro-IL-1β and pro-IL-18, resulting in the production of mature IL-1β and IL-18 1.
- Elevated levels of IL-1β and IL-18 can contribute to inflammation and tissue damage in various diseases, including ischemic stroke and MAS 1.
Clinical Implications
- The measurement of IL-1β and IL-18 levels may be useful in diagnosing and monitoring diseases associated with NLRP3 activation, such as MAS 1.
- Therapeutic strategies targeting the NLRP3 inflammasome and IL-1β and IL-18 production may be effective in reducing inflammation and tissue damage in these diseases 1.
From the Research
NLRP3 Activation and IL-1β and IL-18 Levels
- Elevated levels of Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18) are associated with NLRP3 (Nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3) activation, as they are both pro-inflammatory cytokines that are processed and secreted upon activation of the NLRP3 inflammasome 2, 3, 4, 5, 6.
- The NLRP3 inflammasome is a multiprotein complex that activates caspase-1, leading to the processing and secretion of IL-1β and IL-18, which have both shared and unique biological functions 2, 3, 4, 5.
- The ratio between IL-1β and IL-18 can be used to describe the NLRP3 inflammasome response, as different stimuli can induce different ratios of these cytokines 2.
Mechanism of NLRP3 Activation
- The mechanism of NLRP3 activation involves the generation of reactive oxygen species (ROS), which is a crucial element for NLRP3 activation 3.
- The NLRP3 inflammasome can be activated by diverse stimuli, including microorganisms and metabolic dysregulation, and its activation leads to the maturation of IL-1β and IL-18 and the induction of pyroptosis, a form of cell death 3, 5.
Clinical Implications
- Elevated levels of NLRP3, IL-1β, and IL-18 have been observed in patients with diabetic nephropathy, and their levels increase with the aggravation of the disease 6.
- The plasma levels of NLRP3, IL-1β, and IL-18 can be useful as indicators of the occurrence and development of diabetic nephropathy and can provide clinical guidance for the early diagnosis and treatment of the disease 6.