Endogenous Interleukin 18 Suppresses Hyperglycemia and Hyperinsulinemia during the Acute Phase of Endotoxemia in Mice

Yamashita, Hayato; Ishikawa, Michiko; Takahara, Miki; Yamauchi, Chisato; Inoue, Taketo; Miyoshi, Makoto; Maeshige, Noriaki; Usami, Makoto; Nakao, Atsunori; Kotani, Joji

doi:10.1089/sur.2013.269

Cited by 6 publications

(7 citation statements)

References 28 publications

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“…Moreover, similar associations were found in studies on the impact of postprandial hyperglycemia and hypertriglyceridemia on endothelial inflammation [45][46][47]. IL-18 may attenuate lipid metabolism, postprandial hyperglycemia, and modulate insulin signalling [45] and by triggering endothelial inflammation, promote the formation of atherosclerotic plaques [45][46][47].…”

Section: Discussionsupporting

confidence: 70%

Associations of IL-18 with Altered Cardiovascular Risk Profile in Psoriatic Arthritis and Ankylosing Spondylitis

Bonek

Kuca-Warnawin

Kornatka

et al. 2022

JCM

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Objective: To investigate the associations of IL-18 serum levels with serum lipids, cardiovascular risk, and disease activity in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with axial (axPsA) and peripheral (perPsA) joint involvement. Methods: 155 adult patients (PsA 61/AS 94) were enrolled in the study. Standard disease activity indices, BASDAI, and ASDAS, were calculated for AS and PsA and DAPSA for PsA. Sera from peripheral blood samples were obtained after night fasting. Serum concentrations of cytokines (IL-18, IL-17) were measured by ELISA, while lipid profile with total cholesterol (TC), triglycerides (TG), low-density cholesterol-(LDL), high-density cholesterol (HDL), and C-reactive protein (CRP) concentrations were determined using routine procedures. The atherogenic index was calculated using the standard formula AI = TC/HDL. Results: Patients with PsA and peripheral joint involvement (perPsA) had significantly higher IL-18 serum levels than axial PsA and AS patients (medians 160 vs. 116 vs. 80 pg/mL). In patients with PsA and in the subgroup with PsA+ ischemic heart disease (IHD), IL-18 positively correlated with atherogenic index (AI) (rho = 0.46 and rho = 0.67, respectively) and TG serum concentrations (rho = 0.4 and rho = 0.675), while negatively with HDL levels (rho= −0.37 and rho= −0.608). In PsA + IHD subgroup IL-18 serum levels correlated positively also with disease activity (DAPSA) (rho = 0.613). Importantly, in patients with perPsA, characterized by the highest IL-18 serum levels, cardiovascular risk, and frequency of both hypertriglyceridemia and IHD, positive correlations between IL-18 and IL-17 (rho = 0.47, p = 0.002), TG (rho = 0.45 p = 0.01) levels and AI (rho = 0.63 p = 0.021) were found. Whereas linear regression models revealed that IL-17, TG concentrations and the tender joint count had an impact on IL-18 Conclusions: We confirmed that patients with perPsA are characterized by a more pronounced proinflammatory and proatherogenic cardiovascular risk profile than patients with axPsA and AS. Importantly our study indicates that in PsA, but not in AS, elevated serum concentration of IL-18 is associated with higher disease activity and proatherogenic lipid profile, leading to a higher cardiovascular risk. Thus, our results point out IL-18 as a critical contributor in these pathological processes and possible therapeutic targets.

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Section: Discussionsupporting

confidence: 70%

Associations of IL-18 with Altered Cardiovascular Risk Profile in Psoriatic Arthritis and Ankylosing Spondylitis

Bonek

Kuca-Warnawin

Kornatka

et al. 2022

JCM

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“…Additionally, septic patients suffering acute respiratory distress syndrome (ARDS) had higher plasma IL-18 levels than septic patients without ARDS (13). In our previous report, which was the first report focusing on IL-18 and transient insulin resistance mediated by acute inflammation, we found that endogenous IL-18 attenuated transient hyperglycemia by enhancing hepatic insulin signaling during the hyperacute phase of lipopolysaccharide (LPS)-induced lethal endotoxemia (14).…”

Section: Il-18 Is a Pro-inflammatory Cytokine Secreted By T-cells Mamentioning

confidence: 96%

“…Western blotting was performed as described previously (14). was determined in a previous study (17).…”

Section: Blood Analysismentioning

confidence: 99%

Interleukin-18 Reduces Blood Glucose and Modulates Plasma Corticosterone in a Septic Mouse Model

Yamashita

Ishikawa

Inoue

et al. 2017

Shock

Self Cite

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“…Moreover, there is a relationship between hyperglycemia and altered cellular metabolism in critically ill patients that results in insulin resistance and release of systemic in ammatory mediators [6]. Earlier studies suggested that proin ammatory cytokines such as interleukin (IL)-6 and IL-18 are involved in glucose metabolism and insulin action; therefore, hypercytokinemia may have a potential role in increased glucose levels [6,12,13]. This indicates that immunoneuroendocrine alterations might be involved in the pathophysiology of SIH during acute illnesses [14].…”

Section: Introductionmentioning

confidence: 99%

Patterns and Effects of Admission Hyperglycemia And Inflammatory Response in Trauma Patients: A Prospective Study

El‐Menyar

Asim

Mir

et al. 2020

Preprint

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Background: Hyperglycemia following trauma could be a response to stress. The constellation of the initial hyperglycemia, proinflammatory cytokines and severity of injury among trauma patients is understudied. We aimed to evaluate the patterns and effects of on-admission hyperglycemia and inflammatory response in a level 1 trauma center admissions. Methods: A prospective, observational study was conducted for adult trauma patients who were admitted and tested for on-admission blood glucose, hemoglobin A1c, interleukin (IL)-6 ,Il-18 and hs-CRP. Patients were categorized into 4 groups (non-diabetic normoglycemic, diabetic normoglycemic, diabetic hyperglycemic (DH) and stress-induced hyperglycemic (SIH)). The inflammatory markers were measured on 3 time points (admission, 24 h, and 48 h). Pearson’s correlation test and logistic regression analysis were performed. We hypothesized that higher initial readings of blood glucose and cytokines are associated with severe injuries and worse in-hospital outcomes in trauma patients.Results: During the study period, 250 adult trauma patients were enrolled. Almost 13% of patients presented with hyperglycemia (SIH&DH); of whom 50% had SIH. Compared to the other 3 groups; SIH patients were younger, had significantly higher ISS, higher IL-6 readings, prolonged hospital length of stay and higher mortality. The SIH group had lower Revised Trauma Score (p=0.005), lower Trauma Injury Severity Score (p=0.01) and lower GCS (p=0.001). IL-18 and hs-CRP were comparable among the study groups. Compared to the normoglycemia groups, patients with hyperglycemia had elevated high- sensitive troponin T (p=0.001) and required more blood transfusion (p=0.03). Patients with hyperglycemia had 3-times higher in-hospital mortality than the normoglycemia groups (p=0.02). A significant correlation was identified between initial blood glucose and serum lactate, IL-6, ISS and hospital length of stay. IL-6 correlated well with ISS (r=0.40, p=0.001). On- admission blood glucose had age-sex-GCS adjusted odd ratio 1.20(95% CI 1.06-1.33, p=0.003) for severe injury (ISS≥16).Conclusions: On-admission hyperglycemia is associated with a significant severer injury than normoglycemia patients. Initial blood glucose correlates with serum IL-6 which indicates a potential role of the systemic inflammatory response in the disease pathogenesis among the injured patients. On-admission glucose level could be a useful marker of injury severity, triage and risk assessment in trauma patients.This study was registered at the ClinicalTrials.gov (Identifier: NCT02999386), retrospectively Registered on December 21, 2016 https://clinicaltrials.gov/ct2/show/NCT02999386.

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Endogenous Interleukin 18 Suppresses Hyperglycemia and Hyperinsulinemia during the Acute Phase of Endotoxemia in Mice

Cited by 6 publications

References 28 publications

Associations of IL-18 with Altered Cardiovascular Risk Profile in Psoriatic Arthritis and Ankylosing Spondylitis

Associations of IL-18 with Altered Cardiovascular Risk Profile in Psoriatic Arthritis and Ankylosing Spondylitis

Interleukin-18 Reduces Blood Glucose and Modulates Plasma Corticosterone in a Septic Mouse Model

Patterns and Effects of Admission Hyperglycemia And Inflammatory Response in Trauma Patients: A Prospective Study

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