Impairment of Helper T-Cell Function Following Severe Head Injury

Quattrocchi, Keith B.; Issel, Bernardo W.; Miller, Claramae H.; Frank, Edmund; Wagner, Franklin C.

doi:10.1089/neu.1992.9.1

Cited by 89 publications

(22 citation statements)

References 42 publications

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“…In addition, HDL particles reverse the inhibitory action of oxidized LDL particles on endothelium-dependent arterial relaxation [41] and also inhibit cytokine-induced expression of endothelial cell adhesion molecules [42]; both of which may be potential mechanisms in the development of VaD. Oxidative stress and lipid oxidation in particular have a pivotal role in the development of VaD [43]; lipid peroxidation may influence neuronal membrane permeability, affecting cellular function and damaging membrane-bound receptors and enzymes [44]. The brain may be particularly susceptible to oxidative lipid damage due to its high content of polyunsaturated fatty acids [44].…”

Section: Lipid Effects On Vascular Dementiamentioning

confidence: 99%

“…Oxidative stress and lipid oxidation in particular have a pivotal role in the development of VaD [43]; lipid peroxidation may influence neuronal membrane permeability, affecting cellular function and damaging membrane-bound receptors and enzymes [44]. The brain may be particularly susceptible to oxidative lipid damage due to its high content of polyunsaturated fatty acids [44]. Paraoxonase 1 is an A-esterase with peroxidase-like activity present on the surface of HDL, which decreases peroxidation of LDL.…”

Section: Lipid Effects On Vascular Dementiamentioning

confidence: 99%

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Hypercholesterolaemia and vascular dementia

et al. 2017

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Correspondence: Philip Bath (Philip.bath@nottingham.ac.uk) Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors -diabetes, hypercholesterolaemia, hypertension and smoking -are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet not fully understood. Similarly, the effects of lipids and lipid-lowering therapy on preventing or treating dementia remain unclear; the few trials that have assessed lipid-lowering therapy for preventing (two trials) or treating (four trials) dementia found no evidence to support the use of lipid-lowering therapy for these indications. It is appropriate to treat those patients with vascular risk factors that meet criteria for lipid-lowering therapy for the primary and secondary prevention of cardiovascular and cerebrovascular events, and in line with current guidelines. Managing the individual patient in a holistic manner according to his or her own vascular risk profile is recommended. Although the paucity of randomized controlled evidence makes for challenging clinical decision making, it provides multiple opportunities for on-going and future research, as discussed here.

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Section: Lipid Effects On Vascular Dementiamentioning

confidence: 99%

Section: Lipid Effects On Vascular Dementiamentioning

confidence: 99%

Hypercholesterolaemia and vascular dementia

et al. 2017

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“…Head injury is followed by an almost immediate drop of lymphocyte numbers that is accompanied by a deficit in T-cell activation and decreased CD25 expression. These changes seem to persist up to several weeks after TBI [21,34,35]. β2m is a small glycoprotein and elevated levels of the soluble form are thought to reflect the release by activated lymphocytes and neutrophils [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, T-cell numbers and function remain suppressed for up to 3 weeks after injury [21,34,35]. However, elevations of sIL-2R and neopterin, representing a sustained activation of the IFN-γ and TNF pathways, are not necessarily synonymous for an efficient immune response [36].…”

Section: Discussionmentioning

confidence: 99%

Low T3 Syndrome in Head-Injured Patients is Associated with Prolonged Suppression of Markers of Cell-Mediated Immune Response

et al. 2005

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European Journal of Trauma Ab stractPurpose: To clarify the association between disturbed thyroid hormone metabolism (low T 3 syndrome) and release of cytokines and markers of cell-mediated immune response. Material and Methods: Concentrations of cytokines as well as of thyroid hormones were determined in 32 patients suffering from severe traumatic brain injury: interleukin-(IL-)1, IL-6, IL-10, tumor necrosis factor, transforming growth factor-(TGF-)β, soluble interleukin-2 receptor (sIL-2R), neopterin, and β 2 -microglobulin (β2m) in serum and cerebrospinal fluid; triiodothyronine (T 3 ), free T 3 , thyroxine (T 4 ), free T 4 , thyrotropin, thyroxine-binding globulin, and albumin in serum. Additionally, clinical parameters were assessed: Glasgow Coma Score, CT scan, intracranial pressure, Glasgow Outcome Score, and occurrence of pneumonia. Results: Among 31 patients with a low T 3 syndrome, those with additional low serum T 4 levels (n = 13) showed a prolonged suppression of serum β2m, neopterin, and sIL-2R, and a higher secondary increase of serum β2m, neopterin, and TGF-β, as well as lower T 3 levels (all p < 0.05). These patients also had a longer stay in the intensive care unit (34 ± 6 days vs. 22 ± 12 days; p = 0.008). Increased levels of β2m correlated with a preceding decrease of thyrotropin (cerebrospinal fluid: r = -0.53; p = 0.004; serum: r = -0.41; p = 0.029). Associations of thyroid hormone metabolism with either other cytokines or with clinical parameters were not detected. Conclusion:These results show that low T3 syndrome is a very common pathophysiological feature after severe traumatic brain injury. The association of a low T 3 syndrome in combination with low serum T 4 levels, with an altered time course of markers of cell-mediated immunity led the authors to hypothesize that a disturbed thyroid hormone metabolism may be interrelated with a prolonged cellular immune dysfunction after traumatic brain injury.

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“…After severe head injury, decreased T-helper cell activation, attenuated lymphokine-activated killer cell cytotoxicity, and depression of proinflamma-tory cytokine production (IL-2, IFN-␥), have been reported. [9][10][11][12][13][14] Moreover, ex vivo whole blood stimulation with lipopolysaccharide (LPS) shows an attenuated production of proinflammatory cytokines TNF␣, IL-1␤, IL-6, IL-8, IFN-␥, and IL-12 in polytrauma patients compared to healthy controls. 15 Another study demonstrated decreased TNF␣ mRNA levels in human peritoneal macrophages after polytrauma, while the antiinflammatory cytokine IL-10 was upregulated.…”

Section: Immune Paralysis In Patients With Tbimentioning

confidence: 99%

Increased vagal tone accounts for the observed immune paralysis in patients with traumatic brain injury

Kox¹,

Pompe²,

Pickkers³

et al. 2008

Neurology

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Traumatic brain injury (TBI) is a leading cause of death and disability, especially in the younger population. In the acute phase after TBI, patients are more vulnerable to infection, associated with a decreased immune response in vitro. The cause of this immune paralysis is poorly understood. Apart from other neurologic dysfunction, TBI also results in an increase in vagal activity. Recently, the vagus nerve has been demonstrated to exert an anti-inflammatory effect, termed the cholinergic anti-inflammatory pathway. The anti-inflammatory effects of the vagus nerve are mediated by the ␣7 nicotinic acetylcholine receptor present on macrophages and other cytokineproducing cells. From these observations, we hypothesize that the immune paralysis observed in patients with TBI may, at least in part, result from augmented vagal activity and subsequent sustained effects of the cholinergic anti-inflammatory pathway. This pathway may counteract systemic proinflammation caused by the release of endogenous compounds termed alarmins as a result of tissue trauma. However, sustained activity of this pathway may severely impair the body's ability to combat infection. Since the cholinergic anti-inflammatory pathway can be pharmacologically modulated in humans, it could represent a novel approach to prevent infections in patients with TBI. Neurology

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Impairment of Helper T-Cell Function Following Severe Head Injury

Cited by 89 publications

References 42 publications

Hypercholesterolaemia and vascular dementia

Hypercholesterolaemia and vascular dementia

Low T3 Syndrome in Head-Injured Patients is Associated with Prolonged Suppression of Markers of Cell-Mediated Immune Response

Increased vagal tone accounts for the observed immune paralysis in patients with traumatic brain injury

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