Abstract
Blocking the cytokines Interleukin-1beta (IL-1β) and Interleukin-18 (IL-18) benefits a diverse range of inflammatory pathologies. In each of these diseases, different cytoplasmic innate immune receptors nucleate individual protein complexes known as inflammasomes, to regulate the production of active IL-1β or IL-18. This review will outline the complex diseases where these cytokines are pathogenic, and explain which inflammasome(s) may be responsible. For example, inflammasomes nucleated by NLRP3 and NLRP6 integrate signals from metabolic and commensal systems contributing to metabolic dysfunction and type 2 diabetes. On the other hand, NLRP1 and AIM2 are more broadly implicated in autoimmunity and allergy. Furthermore, each inflammasome has unique roles in pathogen recognition, which may determine the outcome of polymicrobial infection and link different infectious co-morbidities to chronic inflammatory disease. We can now imagine a time when targeted inflammasome inhibitors will be employed in the clinic, tailoring treatments to particular diseases, and perhaps individual patients.
Copyright © 2012 Elsevier Inc. All rights reserved.
MeSH terms
-
Adaptor Proteins, Signal Transducing / metabolism
-
Alzheimer Disease / genetics
-
Alzheimer Disease / immunology
-
Alzheimer Disease / metabolism
-
Animals
-
Apoptosis Regulatory Proteins / metabolism
-
Atherosclerosis / genetics
-
Atherosclerosis / immunology
-
Atherosclerosis / metabolism
-
Carrier Proteins / metabolism*
-
DNA-Binding Proteins
-
Diabetes Mellitus, Type 2 / immunology
-
Diabetes Mellitus, Type 2 / metabolism
-
Gout / genetics
-
Gout / immunology
-
Gout / metabolism
-
Humans
-
Inflammasomes / immunology*
-
Inflammatory Bowel Diseases / genetics
-
Inflammatory Bowel Diseases / immunology
-
Inflammatory Bowel Diseases / metabolism
-
Interleukin-18 / metabolism*
-
Interleukin-1beta / metabolism*
-
Intracellular Signaling Peptides and Proteins / immunology
-
Intracellular Signaling Peptides and Proteins / metabolism*
-
NLR Family, Pyrin Domain-Containing 3 Protein
-
NLR Proteins
-
Neoplasms / genetics
-
Neoplasms / immunology
-
Neoplasms / metabolism
-
Nuclear Proteins / genetics
-
Nuclear Proteins / immunology
-
Obesity / genetics
-
Obesity / immunology
-
Obesity / metabolism
Substances
-
AIM2 protein, human
-
Adaptor Proteins, Signal Transducing
-
Apoptosis Regulatory Proteins
-
Carrier Proteins
-
DNA-Binding Proteins
-
Inflammasomes
-
Interleukin-18
-
Interleukin-1beta
-
Intracellular Signaling Peptides and Proteins
-
NLR Family, Pyrin Domain-Containing 3 Protein
-
NLR Proteins
-
NLRP1 protein, human
-
NLRP3 protein, human
-
NLRP6 protein, human
-
Nuclear Proteins