Pharmacological control of inflammation via innate immune memory manipulation
Abstract
Chronic inflammation underlies several common diseases although it is inadequately managed by conventional anti-inflammatory therapies that often suppress immune responses and have long-term adverse effects. Innate immune memory encompasses trained immunity and tolerance, which provide a comprehensive framework for persistent maladaptive innate responses that drive the pathogenesis of neurodegenerative disorders, oncological, cardiometabolic, and autoimmune diseases. This Invited Mini-Review elucidates the molecular mechanisms of innate immune memory including epigenetic reprogramming of chromatin configurations, metabolic rewiring towards glycolytic or oxidative metabolic pathways and the signaling of pattern recognition receptors (PRRs) and the NLRP3 inflammasome that reinforce either enhanced or diminished innate responsiveness. We subsequently discuss pharmacological strategies for selective modulation of innate immune memory. Epigenetic modulators including histone deacetylase (HDAC) and Bromodomain and Extra- Terminal Domain (BET) inhibitors may modify aberrant chromatin programs, while metabolic modulators like metformin and statins can influence their cellular bioenergetics and inflammatory response. Direct NLRP3 inflammasome inhibitors including MCC950 and INF-39 target maladaptive NLRP3 inflammasome signaling. MCC 950 was stopped at the preclinical stage due to hepatotoxicity. Early clinical studies of trained immunity include Bacillus Calmette-Guerin (BCG) vaccine…
Read the paper
Related studies
- Diarylethenes for Memories and Switches
- Long-Term Potentiation and Memory
- Social Memory Studies: From “Collective Memory” to the Historical Sociology of Mnemonic Practices
- The Cognitive Neuroscience of Working Memory
- Memory aging and brain maintenance
- Effector and Memory CTL Differentiation
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.