The role of endogenous interleukin-1 in stress-induced adrenal activation and adrenalectomy-induced adrenocorticotropic hormone hypersecretion

To examine the role of IL-1 in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis, mice with knockout of the IL-1 receptor type I (IL-1rKO) were exposed to psychological and metabolic stressors. When exposed to mild stressors (auditory stress or a low dose of 2-deoxyglucose), IL-1rKO mice displayed a significantly diminished corticosterone secretion, compared with wild-type (WT) controls. In response to more severe stressors (60-min restraint or a high dose of 2-deoxyglucose), both groups exhibited a similar increase in corticosterone secretion. To examine the role of IL-1 in HPA axis feedback regulation, serum ACTH levels were measured after adrenalectomy (ADX) in IL-1rKO mice and in mice with transgenic overexpression of IL-1 receptor antagonist within the brain (IL-1raTG). As expected, WT controls exhibited ADX-induced ACTH hypersecretion, whereas IL-1rKO and IL-1raTG mice showed no increase in ACTH levels, suggesting that brain IL-1 has a critical role in ADX-associated ACTH hypersecretion. Similarly, WT mice that were chronically exposed to IL-1ra in utero displayed a diminished ADX-induced ACTH hypersecretion, compared with vehicle-treated controls, suggesting a developmental role of IL-1 in HPA axis regulation. In conclusion, our results suggest that endogenous IL-1 plays a critical role in HPA axis activation after stress and ADX.     

Higher Neutrophil/Lymphocyte Ratio Is Related to Lower Ejection Fraction and Higher Long-term All-Cause Mortality in ST-Elevation Myocardial Infarction Patients

Background

Neutrophil/lymphocyte ratio (NLR) is a novel biomarker that can single out individuals at risk for vascular events. We assessed whether NLR provides additive prognostic value in patients with ST-elevation myocardial infarction (STEMI).

Methods

NLR was computed from the absolute values of neutrophils and lymphocytes from the complete blood count of patients who underwent primary coronary angioplasty for STEMI. The cohort was divided into 2 groups according to NLR (NLR ≥ 6.5%, NLR < 6.5%) using χ² automatic interaction detection. The association between NLR and in-hospital clinical complications and left ventricular ejection fraction (EF) was assessed using logistic regression. The association between NLR, 30-day and 5-year all-cause mortality were analyzed using Cox regression models, adjusting for potential clinical, metabolic, and inflammatory confounders.

Results

In a group of 538 consecutive STEMI patients, high NLR (NLR ≥ 6.5%) was independently associated with increased 30-day and 5-years mortality rates (odds ratio, 15.8; 95% confidence interval, 1.6-154; P = 0.018; and hazard ratio, 2.2; 95% confidence interval, 1.04-4.8; P = 0.039, respectively). High NLR was also independently associated with lower EF (49 ± 8 vs 46 ± 8; P < 0.001) and fewer hospital complications.

Conclusions

In patients presenting with STEMI, high NLR was independently associated with lower EF, fewer hospital complications, and higher mortality rates up to 5 years. NLR value appears additive to conventional risk factors and commonly used biomarkers.