scholarly journals Insulin Allergy and Immunologic Insulin Resistance Caused by Interleukin-6 in a Patient With Lung Cancer

Diabetes Care ◽  
2006 ◽  
Vol 29 (7) ◽  
pp. 1711-1712 ◽  
Author(s):  
S. Mizuhashi ◽  
K. Nakamura ◽  
Y. Mori ◽  
M. Noda ◽  
K. Nakanishi
2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 989.3-989
Author(s):  
A. Jitaru ◽  
C. Pomirleanu ◽  
M. M. Leon-Constantin ◽  
F. Mitu ◽  
C. Ancuta

Background:Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, due not only to the traditional risk factors (hypertension, insulin resistance/diabetes, obesity, smoking), but to the inflammatory status as well. The blockade of interleukin-6 (IL-6) can regulate the glucose metabolism, reducing the glucose level and insulin resistance (IR). This beneficial effect is seen more in patients with normal values of body mass index (BMI), compared to the obese population.Objectives:Given the mentioned existing data, we aim to demonstrate the positive effect of IL-6 inhibitors in active RA patients with normal or increased BMI.Methods:We recruited 56 consecutive patients with definite and active RA, non-responders/partial responders to conventional synthetic Drug Modifying Anti-Rheumatic Drugs (csDMARDs)/biological therapy. For a period of 52 weeks, patients received subcutaneous Tocilizumab (TCZ) in a dose of 162mg once a week, according to European League Anti Rheumatism (EULAR) recommendation and National Protocol. We assessed demographics, RA-related parameters (clinical, inflammatory and immune) and metabolic markers, as well as the peripheral response to insulin, quantified by Homeostasis Model Assessment for insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). We did not include in the study the patients known with diabetes mellitus (DM) and those undergoing glucocorticoids.Results:After 52 weeks of treatment, most of the patients showed a statistically significant reduction of HOMA-IR (3.61 ± 1.21 at the onset vs. 2.45 ± 1.46 at the end of the study, p<0.001), while QUICKI registered a slight increase (0.32 ± 0.01 at the onset vs. 0.33 ± 0.01 at the end of the study, p<0.001). Also, the decrease in insulin and glucose levels were more obvious in patients with normal BMI, strictly related to disease activity.Conclusion:Long-term administration of TCZ in active RA is associated with a significant reduction of disease activity and IR, especially in normal weight patients. This confirms that obesity, as a CV risk factor, represents one of the main causes of IR.References:[1]Castañeda S, Remuzgo-Martínez S, López-Mejías R et al. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis.Clin Exp Rheumatol. 2019; 37(3):465-473.[2]Lehrskov LL, Christensen RH. The role of interleukin-6 in glucose homeostasis and lipid metabolism.Semin Immunopathol. 2019; 41(4):491-499.[3]Ursini F, Russo E, Ruscitti P, Giacomelli R, De Sarro G. The effect of non-TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis.Autoimmun Rev. 2018 Apr;17(4):399-404.Disclosure of Interests:Alexandra Jitaru: None declared, Cristina Pomirleanu: None declared, Maria-Magdalena Leon-Constantin: None declared, Florin Mitu: None declared, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly


2003 ◽  
Vol 278 (16) ◽  
pp. 13740-13746 ◽  
Author(s):  
Joseph J. Senn ◽  
Peter J. Klover ◽  
Irena A. Nowak ◽  
Teresa A. Zimmers ◽  
Leonidas G. Koniaris ◽  
...  

2007 ◽  
Vol 8 (1) ◽  
pp. 46
Author(s):  
L. Carulli ◽  
I. Canedi ◽  
S. Rondinella ◽  
D. Ganazzi ◽  
S. Fargion ◽  
...  

Author(s):  
Jae-Hyun Jang ◽  
Donghwan Park ◽  
Guen-soo Park ◽  
Dong-Wook Kwak ◽  
JaeIn Park ◽  
...  

AbstractAlthough lung cancer is the leading cause of cancer-related deaths worldwide and KRAS is the most frequently mutated oncogene in lung cancer cases, the mechanism by which KRAS mutation drives lung cancer has not been fully elucidated. Here, we report that the expression levels of leukotriene B4 receptor-2 (BLT2) and its ligand-producing enzymes (5-LOX, 12-LOX) were highly increased by mutant KRAS and that BLT2 or 5-/12-LOX blockade attenuated KRAS-driven lung cell proliferation and production of interleukin-6 (IL-6), a principal proinflammatory mediator of lung cancer development. Next, we explored the roles of BLT2 and 5-/12-LOX in transgenic mice with lung-specific expression of mutant KRAS (KrasG12D) and observed that BLT2 or 5-/12-LOX inhibition decreased IL-6 production and tumor formation. To further determine whether BLT2 is involved in KRAS-driven lung tumor formation, we established a KrasG12D/BLT2-KO double-mutant mouse model. In the double-mutant mice, we observed significantly suppressed IL-6 production and lung tumor formation. Additionally, we observed high BLT2 expression in tissue samples from patients with KrasG12D-expressing lung adenocarcinoma, supporting the contributory role of BLT2 in KRAS-driven human lung cancer. Collectively, our results suggest that BLT2 is a potential contributor to KRAS-driven lung cancer and identify an attractive therapeutic target for KRAS-driven lung cancer.


2016 ◽  
Vol 53 (5) ◽  
pp. 268
Author(s):  
Raynald Takumansang ◽  
Sarah M. Warouw ◽  
Hesti Lestari

Background Obesity has become a rapidly growing epidemic worldwide, increasing the risk of morbidity and mortality in adolescents. Obesity is due to an expansion of adipose tissue mass, which is an important source of cytokines and contributes to an increase in pro-inflammatory cytokines, such as interleukin-6 (IL-6). Interleukin-6 is significantly increased in obesity and may lead to a state of insulin resistance.Objective To assess for a correlation between IL-6 levels and insulin resistance in obese adolescentsMethods We conducted a cross-sectional study from January to April 2012 in Manado, North Sulawesi. Subjects were either obese or normal body mass index (BMI) teens aged 13-18 years. Data collected were anthropometric status, BMI, and blood specimens for fasting plasma glucose levels, fasting insulin levels, and IL-6 levels. Insulin resistance was expressed as homeostatic model assessment of insulin resistance (HOMA-IR) level >2.77. Data was analyzed by Pearson’s correlation and linear regression tests to assess for a possible correlation between IL-6 levels and insulin resistance.Results The mean BMI in the obese group was 31.21 (SD 3.61) kg/m2 while the mean BMI in the normal group was 19.52 (SD 2.38) kg/m2. There was no significant association between IL-6 and the occurrence of insulin resistance (P=0.309). The log regression coefficient value of IL-6 was negative (b = -0.329).Conclusion There is no correlation between IL-6 levels and incidence of insulin resistance in obese adolescents.


2020 ◽  
Vol 105 (10) ◽  
pp. e3757-e3765
Author(s):  
Anthony S Zannas ◽  
Jennifer L Gordon ◽  
Alan L Hinderliter ◽  
Susan S Girdler ◽  
David R Rubinow

Abstract Objective Cardiometabolic diseases are the number one cause of mortality, accounting for over one third of all deaths in the United States. Cardiometabolic risk further increases with psychosocial stress exposure and during menopausal transition in women. Because disease risk and stress burden are associated with aberrant immune signaling, we hypothesized that responses of interleukin-6 (IL-6) to psychosocial stress may predict longitudinal cardiometabolic outcomes in perimenopausal women. Methods We conducted post hoc analyses in 151 perimenopausal or early postmenopausal women participants in a previously completed study. At study onset, participants underwent the Trier Social Stress Test (TSST), and plasma IL-6 was measured repeatedly before and during the 1 hour post-TSST. Subsequently, participants were randomly assigned to either hormonal treatment (HT) or placebo and followed for 12 months to determine longitudinal changes in cardiometabolic biomarkers. Results Greater IL-6 reactivity to stress, measured with baseline-adjusted area under the curve, predicted 12-month decrease in flow-mediated dilatation of the brachial artery (P = 0.0005), a measure of endothelial-dependent vascular function, but not in endothelial-independent function measured with nitroglycerin-mediated dilatation (P = 0.17). Greater baseline IL-6 levels predicted 12-month increase in insulin resistance based on the homeostatic model assessment of insulin resistance score (P = 0.0045) and in the number of criteria met for metabolic syndrome (P = 0.0008). These predictions were not moderated by HT. Conclusions Greater baseline IL-6 levels as well as its reactivity to stress may predict worsening in distinct cardiometabolic biomarkers as women transition to menopause. Interleukin-6 reactivity predicts decline in endothelial-dependent vascular function, whereas baseline IL-6 presages accumulation of metabolic risk.


Sign in / Sign up

Export Citation Format

Share Document