Acute Ischemic Stroke is Associated with Increased Serum Levels of Pro-inflammatory Cytokines

Author(s):  
Bhagirath Ramawat ◽  
Alvee Saluja ◽  
Jayashree Bhatacharjee ◽  
Anshuman Srivastava ◽  
Rajinder K. Dhamija
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Coral Torres-Querol ◽  
Pascual Torres ◽  
Noemí Vidal ◽  
Manel Portero-Otín ◽  
Gloria Arque ◽  
...  

AbstractSenescent cells are capable of expressing a myriad of inflammatory cytokines and this pro-inflammatory phenomenon is known as senescence-associated secretory phenotype (SASP). The contribution of this phenomenon in brain ischemia was scarce. A mouse model of transient focal cerebral ischemia by compressing the distal middle cerebral artery (tMCAo) for 60 min was used. SASP, pro-inflammatory cytokines and cell cycle mRNAs levels were quantified at 30-min and 72 h post-surgery. Immunohistochemistry in paraffin embedded human brain slides and mouse brain tissue was performed. Our results showed an increase of both p16 and p21 mRNA restricted to the infarct area in the tMCAo brain. Moreover, there was an induction of Il6, Tnfa, Cxc11, and its receptor Cxcr2 mRNA pro-inflammatory cytokines with a high positive correlation with p16/p21 mRNA levels. The p16 was mainly shown in cytoplasm of neurons and cytoplasm/membrane of microglial cells. The p21 was observed in membrane of neurons and also it showed a mixed cytoplasmic and membranous pattern in the microglial cells. In a human stroke patient, an increase of P16 in the perimeter of the MCA infarct area was observed. These suggest a role of SASP in tMCAo mouse model and in human brain tissue. SASP potentially has a physiological role in acute ischemic stroke and neurological function loss.


2008 ◽  
Vol 41 (16-17) ◽  
pp. 1330-1334 ◽  
Author(s):  
Vanja Basic Kes ◽  
Ana-Maria Simundic ◽  
Nora Nikolac ◽  
Elizabeta Topic ◽  
Vida Demarin

2011 ◽  
Vol 259 (2) ◽  
pp. 400-400 ◽  
Author(s):  
Heidi Ormstad ◽  
Hans Christian Dalsbotten Aass ◽  
Niels Lund-Sørensen ◽  
Karl-Friedrich Amthor ◽  
Leif Sandvik

2008 ◽  
Vol 14 (33) ◽  
pp. 3574-3589 ◽  
Author(s):  
Antonino Tuttolomondo ◽  
Domenico Di Raimondo ◽  
Riccardo di Sciacca ◽  
Antonio Pinto ◽  
Giuseppe Licata

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2086-2086 ◽  
Author(s):  
Saroj Vadhan-Raj ◽  
Xiao Zhou ◽  
Carlos E. Bueso-Ramos ◽  
Shreyaskumar Patel ◽  
Robert S Benjamin ◽  
...  

Abstract Abstract 2086 Background: Anemia in patients with malignancies can be multifactorial including anemia of chronic disease (ACD), also known as anemia of inflammation (AI), and chemotherapy (CT)-induced anemia (CIA) from myelosuppression. Although, exact mechanism for ACD is not known, induction of hepcidin, a key iron-regulatory hormone, by Interleukin (IL)-6 and other pro-inflammatory cytokines with resulting hypoferremia and limitation of iron supply to the bone marrow appear to be major contributors to pathogenesis of anemia. Hepcidin reduces iron levels by inducing degradation of the cellular iron exporter, ferroportin. The objective of this study was to examine the levels of various cytokines/regulators that may play role in ACD. Methods: Chemo-naïve patients with sarcoma scheduled to initiate first-line doxorubicin-based chemotherapy had blood samples drawn at baseline, and following chemotherapy (post cycles1, 3 and 6) for analysis of pro-inflammatory cytokines/other biomarkers of anemia. Serum samples were analyzed for IL-1β, IL-6, TNF-α, Hepcidin, hemojuvelin, ferroportin, soluble transferrin receptor (sTFR), and C-reactive protein (CRP) using ELISA techniques (R&D Diagnostics, Uscn Life Science Inc, or Abnova). Correlations between these biomarkers and Hgb levels at baseline and during the study period were calculated by linear regression analysis (SAS 9.2). Results: Of the 49 patients enrolled on to the clinical trial, there were 26 (53%) women and 23 (47%) men, with median age 45 years (range 19–65 years). Twenty-five percent of the patients had Hgb less than 12g/dL (range, 8.9–15.9 g/dL) prior to CT. At baseline, 50% of the pts had hypoferremia with low serum iron and transferrin saturation <20%. Baseline serum levels of IL-6 (r= −0.73, p<0.0001), hepcidin (r= −0.46, p=0.005), CRP (r= −0.46, p=0.003), sTFR (r= −0.32, p=0.064) inversely correlated with hemoglobin levels prior to CT, supporting their role in ACD. During CT (median 4, range; 1–6 cycles), Hgb declined in all pts with 55% requiring PRBC transfusions (77% of pts starting with baseline Hgb < 12 g/dL vs 47% of pts with baseline Hgb > 12 g/dL). Interestingly, as shown below, Hepcidin, IL-6, and sTFR all significantly negatively correlated with Hgb levels during CT. No significant correlation was found for IL-1β, TNF-α, ferroportin, or hemojuvelin levels with Hgb. Conclusions: IL-6 and Hepcidin pathway appears to play an important role in anemia in cancer patients before and during CT. Treatment with novel agents targeting this pathway may provide effective strategies for prevention and treatment of ACD and CIA. Disclosures: Vadhan-Raj: JNJ: Research Funding.


2015 ◽  
Vol 27 (5) ◽  
pp. 312-316 ◽  
Author(s):  
Chun Yang ◽  
Yukihiko Shirayama ◽  
Ji-Chun Zhang ◽  
Qian Ren ◽  
Kenji Hashimoto

ObjectiveAccumulating evidences suggest that pro-inflammatory cytokines such as interleukin-6 (IL-6) play a role in the pathophysiology of depression. In the learned helplessness (LH) paradigm, ~35% rats are resilient to inescapable stress.MethodsLevels of IL-6 in the serum and medial prefrontal cortex (mPFC) of LH rats (susceptible) and non-LH rats (resilience) were measured using enzyme-linked immunosorbent assay and western blot analysis, respectively.ResultsSerum levels of IL-6 in the LH rats were significantly higher than those of control and non-LH rats. In contrast, tissue levels of IL-6 in the mPFC were not different among three groups.ConclusionThe results suggest that peripheral IL-6 may contribute to resilience versus susceptibility to inescapable stress.


2020 ◽  
Vol 2 (11) ◽  
pp. 5-19
Author(s):  
Megha Agrawal ◽  

Ischemic stroke is a serious medical condition and widely considered one of the most common causes of death and disability in the world today. There have been notable research advances in stroke so far and studies have shown that stroke’s complex pathophysiology process involves the oxidative stress and inflammatory reaction. However, despite the progress in stroke research, currently there are no established biochemical factors available that can be employed in the early diagnostics and intervention in stroke. Mostly, stroke diagnosis is based on neuroimaging, which is not a rapid tool to diagnose stroke. This decreases the survivability rate. Further, conventional therapeutic approaches for ischemic stroke management are based on restoring blood flow to the affected brain area and these therapies are effective only during a limited time window. Hence, this procedure results in benefiting only a very small percentage of patients. In view of these limitations, the ongoing research has focused on seeking alternative treatment methods that can reduce stroke brain damage and improve patients’ outcome. To this end, research goals are targeted towards gaining insights into the inflammatory response triggered by cerebral ischemia that is supposed to play an important role in the progression of stroke, and also the subsequent study of inflammatory molecules in the acute phase of stroke. In this mini-review, we describe the inflammatory processes occurring during ischemic stroke along with the potential for pro-inflammatory cytokines to become stroke biomarkers as well as interesting neuroprotective therapeutic targets that could be blocked or stimulated to modulate inflammation after stroke. Finally, we present a perspective briefly discussing some viewpoints on future studies in the ongoing field of stroke research.


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