In vivo and systems biology studies implicate IL-18 as a central mediator in chronic pain

Abstract

Inflammation is associated with peripheral neuropathy, however the interplay among cytokines, chemokines, and neurons is still unclear. We hypothesized that this neuroinflammatory interaction can be defined by computational modeling based on the dynamics of protein expression in the sciatic nerve of rats subjected to chronic constriction injury. Using Dynamic Bayesian Network inference, we identified interleukin (IL)-18 as a central node associated with neuropathic pain in this animal model. Immunofluorescence supported a role for inflammasome activation and induction of IL-18 at the site of injury. Combined in vivo and in silico approaches may thus highlight novel targets in peripheral neuropathy.

Cardiac Arrest Disrupts Caspase-1 and Patterns of Inflammatory Mediators Differently in Skin and Muscle Following Localized Tissue Injury in Rats: Insights from Data-Driven Modeling

“…Furthermore, we observed larger quantities of IL-18 vs. IL-1β, in line with reported requirement for prestimulation, for example with LPS, for the detection of large quantities of IL-1β ( 73 ). These findings are also in line with our recent studies in a rat model of chronic constriction injury and neuropathic pain ( 42 ).…”

“…More recently, we have utilized PCA to suggest a key module in a multicompartment mechanistic mathematical model of inflammation and organ pathophysiology in endotoxemic swine ( 48 ), to suggest key physiologic effects of peritoneal suction as a therapy for sepsis ( 32 ), to connect in vitro and in vivo outcomes in the inflammatory response to implanted biomaterials ( 28 ), as well as suggesting key changes in metabolism that occur in the setting of pulsatile perfusion of livers prior to transplantation ( 29 ). Importantly, we have recently used these methods to suggest a role for the inflammasome (including elevated IL-18 and caspase-1) in a rat model of chronic neuropathic pain ( 42 ).…”

“…We have previously shown the preservation of animal and human tissues in RNALater™ (Ambion, Austin, TX, USA) is a method compatible with subsequent Luminex™ analysis ( 40 – 42 ). Accordingly, all tissue samples were sectioned into ≤0.5 cm 3 pieces and placed into individual sample tubes filled with RNALater™ and stored as per manufacturer instructions and as determined empirically in our prior study ( 40 ).…”

Inflammatory markers are associated with cardiac autonomic dysfunction in recent-onset type 2 diabetes

“…With respect to diabetes-related complications, a recent meta-analysis showed that high IL-18 levels are associated with an increased risk for non-fatal myocardial infarction or death from coronary heart disease independently of conventional cardiovascular risk factors 11. IL-18 has also been implicated in neuroinflammation and pain 12 13. Underlining the biological plausibility of our finding, IL-18 release can be downregulated by the PSNS under certain experimental condition 12.…”

Comment on “In vivo and systems biology studies implicate IL-18 as a central mediator in chronic pain” by Vasudeva et al., J. Neuroimmunol. 2015 June; 283:3–49

“…We read with great interest the excellent work of Vasudeva et al (2015) who investigated the role of cytokines and chemokines in a rat chronic constriction injury model. In vivo investigation and Dynamic Bayesian Network modelling identified interleukin-18 (IL-18) as a central node associated with neuropathic pain, and interferon gamma (IFN-γ) and interleukin-1 beta (IL-1β) as central nodes associated with tissue injury.…”