Immune responses after acute ischemic stroke or myocardial infarction

Hæusler, Karl Georg; Schmidt, W. U.; Foehring, Fabian; Meisel, Christian; Guenther, Christoph; Brunecker, Peter; Kunze, Claudia; Helms, Thomas M.; Dirnagl, Ulrich; Volk, Hans‐Dieter; Villringer, Arno

doi:10.1016/j.ijcard.2010.10.053

Cited by 53 publications

(36 citation statements)

References 37 publications

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“…3,[25][26][27][28] Such therapeutical approaches may include intensified screening for infections and more liberal use of anti-infective agents. 29,30 Given various limitations of this study, above findings need to be interpreted with caution. Given that this study lacks a prospective design without specific blood sampling analyses and regimens for diagnosis and treatment of infections weakens the significance of reported associations.…”

Section: Discussionmentioning

confidence: 81%

Lymphocytopenia Is an Independent Predictor of Unfavorable Functional Outcome in Spontaneous Intracerebral Hemorrhage

Giede-Jeppe

Bobinger

Gerner

et al. 2016

Stroke

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Background and Purpose— Stroke-associated immunosuppression is an increasingly recognized factor triggering infections and thus potentially influencing outcome after stroke. Specifically, lymphocytopenia after intracerebral hemorrhage (ICH) has only been addressed in small-sized retrospective studies of mixed intracranial bleedings. This cohort study investigated the natural course of lymphocytopenia, parameters associated with lymphocytopenia on admission (LOA) and during stay, and evaluated the clinical impact of lymphocytopenia in solely ICH patients. Methods— This observational study included 855 consecutive patients with ICH. Patient demographics, clinical and neuroradiological data as well as laboratory and in-hospital measures were retrieved from institutional prospective databases. Functional 3-month outcome was assessed by mailed questionnaires. Lymphocytopenia was defined as <1.0 (10 9 /L) and was correlated with patient’s characteristics and outcome. Results— Prevalence of LOA was 27.3%. Patients with LOA showed significant associations with poorer neurological status (18 [10–32] versus 13 [5–24]; P <0.001), larger hematoma volume (18.5 [6.2–46.2] versus 12.8 [4.4–37.8]; P =0.006), and unfavorable outcome (74.7% versus 63.3%; P =0.0018). Natural course of lymphocyte count during hospital stay revealed a lymphocyte nadir of 1.1 (0.80–1.53 [10 9 /L]) at day 5. Focusing on patients with day-5-lymphocytopenia, compared with patients with LOA, revealed increased rates of infections (63 [71.6] versus 113 [48.5]; P <0.001) and poorer functional outcome at 3 months (76 [86.4] versus 175 [75.1); P =0.029). Adjusting for baseline confounders, multivariable logistic and receiver operating characteristics analyses documented independent associations of day-5-lymphocytopenia with unfavorable outcome (day-5-lymphocytopenia: odds ratio, 2.017 [95% confidence interval, 1.029–3.955], P =0.041; LOA: odds ratio, 1.391 [0.795–2.432], P =0.248; receiver operating characteristics: day-5-lymphocytopenia: area under the curve=0.673, P <0.0001, Youden’s index=0.290; LOA: area under the curve=0.513, P =0.676, Youden’s index=0.084), whereas receiver operating characteristics analyses revealed no association of age or hematoma volume with day-5-lymphocytopenia (age: area under the curve=0.540, P =0.198, Youden’s index=0.106; volume: area under the curve=0.550, P =0.0898, Youden’s index=0.1224). Conclusions— Lymphocytopenia is frequently present in patients with ICH and may represent an independent parameter associated with unfavorable functional outcome. Developing lymphocytopenia affected outcome even stronger than LOA, a finding that may open up new therapeutic avenues in specific subsets of patients with ICH.

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Section: Discussionmentioning

confidence: 81%

Lymphocytopenia Is an Independent Predictor of Unfavorable Functional Outcome in Spontaneous Intracerebral Hemorrhage

Giede-Jeppe

Bobinger

Gerner

et al. 2016

Stroke

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“…This begins a cascade of compensatory anti-inflammatory response. Onset of an acute CNS injury also activates immunoinhibitory pathways, leading to a systemic brain-mediated immunosuppression to minimize secondary damage to healthy CNS tissue (Meisel et al, 2005; Haeusler et al, 2012). Systemic immunosuppression is believed to be the main reason for infections, a leading cause of death in patients with acute CNS injury.…”

Section: Ecs In Sepsismentioning

confidence: 99%

CB2 and GPR55 Receptors as Therapeutic Targets for Systemic Immune Dysregulation

et al. 2016

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The endocannabinoid system (ECS) is involved in many physiological processes and has been suggested to play a critical role in the immune response and the central nervous system (CNS). Therefore, ECS modulation has potential therapeutic effects on immune dysfunctional disorders, such as sepsis and CNS injury-induced immunodeficiency syndrome (CIDS). In sepsis, excessive release of pro- and anti-inflammatory mediators results in multi-organ dysfunction, failure, and death. In CIDS, an acute CNS injury dysregulates a normally well-balanced interplay between CNS and the immune system, leading to increased patients’ susceptibility to infections. In this review, we will discuss potential therapeutic modulation of the immune response in sepsis and CNS injury by manipulation of the ECS representing a novel target for immunotherapy.

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“…Furthermore, there is increasing evidence that reduced monocytic human leukocyte antigen (HLA-DR) expression can independently predict the occurrence of SAI. Even though it is generally accepted that nuclear factor kappa B (NF-κB) activates the expression of various immunological factors, the mechanism underlying their expression after stroke still remains poorly understood [12–13]. …”

Section: Introductionmentioning

confidence: 99%

Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation

et al. 2016

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BackgroundEvidence has led to the consideration of immunodepression after stroke as an important contributor to stroke associated infection (SAI). However, so far no specific immunological indicator has been identified for SAI, and the underlying mechanism remains poorly understood.ResultsSAI patients had significantly higher IL-6 and IL-10 levels and lower HLA-DR levels than no-infection patients within 48h after stroke onset. NA significantly increased IL-10 levels, reduced HLA-DR expression, and decreased IL-6 expression by increasing β-arrestin2 expression which reduced the activation of the NF-κB pathway. Propranolol reversed this effect of NA by reducing β-arrestin2 expression.Materials and MethodsA systematic search for eligible clinical studies was applied to pool the differences in peripheral cytokine levels between infection and no-infection stroke patients. The underlying mechanism behind these differences was investigated in vitro by applying norepinephrine (NA) and lipopolysaccharide (LPS) to simulate sympathetic pathway activation and sepsis respectively in THP-1 cells. Propranolol was applied to determine the effect of reversing the activation of the sympathetic pathway. Immunological indicators were also detected to assess the immune activation of THP-1 cells and measurements of the expression of β-arrestin2, NF-κB, IκBα and phosphor-IκBα were performed to assess the activation of the sympathetic pathway.ConclusionIL-6, IL-10 and HLA-DR are good candidate biomarkers for SAI. The activation of the sympathetic pathway could partly account for the specific immunological alterations found in SAI patients including HLA-DR decrease and IL-10 increase, which both could be reversed by propranolol. However, the mechanism underlying IL-6 increase still needs further exploration.

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Immune responses after acute ischemic stroke or myocardial infarction

Cited by 53 publications

References 37 publications

Lymphocytopenia Is an Independent Predictor of Unfavorable Functional Outcome in Spontaneous Intracerebral Hemorrhage

Lymphocytopenia Is an Independent Predictor of Unfavorable Functional Outcome in Spontaneous Intracerebral Hemorrhage

CB2 and GPR55 Receptors as Therapeutic Targets for Systemic Immune Dysregulation

Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation

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