From the Guidelines
Elevated cystatin C does not have a direct impact on the NLRP3 inflammasome.
Relevant Biomarkers
- Cystatin C is a low-molecular-weight protein produced by all nucleated cells, usually removed by glomerular filtration, and its levels represent a more accurate estimation of GFR 1.
- Biomarkers of renal tubular injury, such as N-acetyl-b-D-glucosaminidase, a-glutathione S-transferase, KIM-1, and neutrophil gelatinase–associated lipocalin (NGAL), are more relevant to renal injury than cystatin C 1.
Clinical Use of Cystatin C
- The combination of serum cystatin C and creatinine has the least bias in the estimation of GFR in cirrhosis 1.
- Cystatin C may add benefit to eGFR estimation, although its levels may be increased by glucocorticoids and inflammation 1.
NLRP3 Inflammasome
- There is no direct evidence in the provided studies that elevated cystatin C affects the NLRP3 inflammasome.
- Markers of inflammation, such as interleukin-18, are more relevant to the NLRP3 inflammasome than cystatin C 1.
From the Research
Elevated Cystatin C and NLRP3 Inflammasome
- The relationship between elevated cystatin C and the NLRP3 inflammasome is not directly addressed in the provided studies.
- However, study 2 suggests that cystatin C deficiency increases the sensitivity to LPS-induced sepsis and NLRP3 inflammasome activation in mice, implying that cystatin C may play a role in regulating the NLRP3 inflammasome.
- Study 3 investigates the role of cystine crystals in activating the NLRP3 inflammasome, but does not directly address the relationship between elevated cystatin C and the NLRP3 inflammasome.
NLRP3 Inflammasome Activation
- The NLRP3 inflammasome is activated by various stimuli, including microbial motifs, endogenous danger signals, and stress signals 4.
- Activation of the NLRP3 inflammasome leads to the formation of a cytosolic multiprotein signaling complex, which serves as a platform for caspase-1 activation and the processing of pro-inflammatory cytokines IL-1β and IL-18 4, 5.
- The NLRP3 inflammasome plays a pivotal role in regulating the innate immune system and inflammatory signaling, and its aberrant activation is involved in various inflammatory diseases 4, 6, 5.
Mechanisms and Inhibitors
- The NLRP3 inflammasome pathway can be targeted by small molecules and biologics to block chronic inflammation and treat various disease pathologies 5.
- Study 6 identifies apolipoprotein C3 as an endogenous inflammasome activator that induces alternative NLRP3 inflammasome activation, highlighting the importance of identifying new anti-inflammatory treatment strategies.
- The development of NLRP3 targeted therapies is an active area of research, with several studies investigating the mechanisms and inhibitors of the NLRP3 inflammasome pathway 4, 5.