Tumor necrosis factor-α: is there a continuum of liability between stress, anxiety states and anorexia nervosa?

Holden, R.J.; Pakula, I.S.

doi:10.1054/mehy.1997.0641

Cited by 35 publications

(24 citation statements)

References 67 publications

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“…In summary, our results are partly in line with previous studies showing increased levels of cytokines TNF-␣ and IL-6 in patients with ED [14,35] . These studies also showed that biological responses to stress, anxiety states and starvation include, for example, elevations of interleukins as an immunological response.…”

Section: Discussionsupporting

confidence: 93%

Levels of Tumour Necrosis Factor-Alpha and Interleukin-6 in Severely Ill Patients with Eating Disorders

Ahrén-Moonga¹,

Lekander²,

Blixen³

et al. 2010

Neuropsychobiology

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Background: The underlying pathophysiology of eating disorders (ED) is dependent on complex interactions between psychological, biological and social factors. The purpose of the present study was to examine a possible increase in cytokines indicating inflammation, as measured by tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in ED patients, and to explore possible relationships between cytokines and self-reported personality traits. Methods: Female patients with severe ED (n = 26) were recruited consecutively from an inpatient clinic and were compared to age-matched healthy females (n = 12). Commercial ELISA tests developed for the measurement of serum levels of TNF-α and IL-6 were employed. Personality traits were measured using Karolinska Scales of Personality. Results: The patient group displayed increased levels of the cytokine TNF-α and a tendency towards increased IL-6 levels. Spearman’s rank correlation coefficient was used to examine possible relationships between levels of cytokines and personality traits. The results showed that IL-6 levels were positively related to both somatic and psychic anxiety and to aggression scales, such as irritability and suspicion. Increased levels of TNF-α, in turn, were significantly correlated with high scores on the depression-related anxiety scale Inhibition of Aggression. However, increased levels of cytokines in the ED group did not seem to be mainly associated with symptoms of depression. Conclusion: We cannot rule out the possibility that comorbid conditions in the group contribute to the higher cytokine values. Further studies need to explore the possible influence of cytokines on the severity of ED and whether this might be mediated or moderated by specific personality traits.

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Section: Discussionsupporting

confidence: 93%

Levels of Tumour Necrosis Factor-Alpha and Interleukin-6 in Severely Ill Patients with Eating Disorders

Ahrén-Moonga¹,

Lekander²,

Blixen³

et al. 2010

Neuropsychobiology

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“…in Nathan and Xie 1994). In this context, it is well known that cytokines are released in brain in animal models of stress (immobilization) (Minami et al 1991;Shintani et al 1995) as well as in plasma samples of humans subjected to psychological stress, anxiety states and anorexia nervosa (Ackerman et al 1998;Holden and Pakula 1999). A corollary of these evidences is that TNF-␣ overproduction resulting from stress-induced TACE up-regulation could mediate the induction of iNOS.…”

Section: Discussionmentioning

confidence: 99%

The Increase in TNF-α Levels Is Implicated in NF-κB Activation and Inducible Nitric Oxide Synthase Expression in Brain Cortex after Immobilization Stress

Madrigal

Hurtado

Moro

et al. 2002

Neuropsychopharmacology

218

120

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The underlying mechanisms by which physical or psychological stress causes neurodegeneration are still unknown. We have demonstrated that the high-output and long-lasting synthesizing source of nitric oxide (NO), inducible NO synthase (iNOS), is expressed in brain cortex after three weeks of repeated stress and that its overexpression accounts for the neurodegenerative changes found in this situation. Now we have found that a short duration of stress (immobilization for 6 h) also induces the expression of iNOS in brain cortex in adult male rats. In order to elucidate the possible mechanisms involved in iNOS expression, we have studied the role of the cytokine tumor necrosis factor-␣ (TNF-␣ ) released in brain during stress. We have shown that there is an increase in soluble TNF-␣ levels after 1 h of stress in cortex and that this is preceded by an increase in TNF-␣ -convertase (TACE) activity in brain cortex as soon as 30 min after immobilization. Stress-induced increase in both TACE activity and TNF-␣ levels seems to be mediated by excitatory amino acids since they can be blocked by MK-801 (dizocilpine) (0.2 mg/kg i.p.), an antagonist of the N-methyl-D-aspartate subtype of glutamate receptor. In order to study the role of TACE and TNF-␣ in iNOS induction, a group of animals were i.p. injected with the preferred TACE inhibitor BB1101 (2 and 10 mg/kg). Indeed, BB1101 inhibited iNOS expression induced by six hours of stress. In addition, we studied the role of the transcription factor nuclear factor B (NF-B), which is Gross and Wolin 1995). In this context, we have demonstrated that restrain stress induces a generalized increase in NO production (Leza et al. 1998) and that iNOS is expressed in brain cortex of rats exposed to stress (Olivenza et al. 2000). In support of the idea that iNOS is one of the mechanisms responsible for the functional damage in this condition, we have also demonstrated that aminoguanidine, a preferred inhibitor of iNOS, protects against cell damage produced by immobilization stress in rats (Olivenza et al. 2000; Madrigal et al. 2000), an experimental procedure used as a model of stress disorders in humans (Bremner et al. 1991).These evidences indicate that stress-induced iNOS expression in brain may mediate, at least in part, the anatomical and clinical features of neurotoxic damage found in animals and humans after exposure to uncontrollable stress (Sheline et al. 1996;Sapolsky 1996;Kim and Yoon 1998). This emphasizes the interest of the study of the mechanisms of iNOS expression after stress exposure. iNOS, as an inducible protein, is mainly regulated at the transcriptional level and is expressed after exposure of cells to several noxious agents such as cytokines and/or lipopolysaccharide (rev. in Nathan and Xie 1994). Although a considerable amount of evidence has shown that physical and psychological stress elevates plasma levels of several cytokines in animals and humans (i.e. TNF-␣ , IL-6, IFN ␥ ), the physiological significance of such elevation remains to be elucidated (Yamasu et a...

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“…The area of infarct, which was unstained, was determined by counting the pixels contained within the outlined regions of interest and expressed in square millimeters. Infarct volumes (in mm 3 ) were integrated from the infarct areas over the extent of the infarct calculated as an orthogonal projection. All animals displayed infarcts after the occlusion procedure, which included the cortex, subcortex, and striatum, depending on the intensity of the lesion.…”

Section: Infarct Sizementioning

confidence: 99%

“…[1][2][3][4] It is accepted that this inflammatory response contributes to the cell damage and death found in neurologic and neuropsychiatric diseases, including those related to stress exposure (depression, posttraumatic stress disorder, etc). 5 In the brain, it has been reported that immobilization stress increases inducible nitric oxide synthase (iNOS) and cyclooxigenase-2 (COX-2) activities and expression and produces an accumulation of lipid peroxidation products.…”

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confidence: 99%

Toll-Like Receptor 4 Is Involved in Subacute Stress–Induced Neuroinflammation and in the Worsening of Experimental Stroke

Caso

Pradillo

Hurtado

et al. 2008

Stroke

172

114

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Background and Purpose-Psychological stress causes an inflammatory response in the brain and is able to exacerbate brain damage caused by experimental stroke. We previously reported that subacute immobilization stress in mice worsens stroke outcome through mechanisms that involve inflammatory mechanisms, such as accumulation of oxidative/nitrosative mediators and expression of inducible nitric oxide synthase and cyclooxygenase-2 in the brain. Some of these inflammatory mediators could be regulated by innate immunity, the activation of which takes place in the brain and produces an inflammatory response mediated by toll-like receptors (TLRs). Recently, we described the implications of TLR4 in ischemic injury, but the role of TLR4 in stress has not yet been examined. We therefore investigated whether inflammation produced by immobilization stress differs in mice that lack a functional TLR4 signaling pathway. Methods-We used an experimental paradigm consisting of the exposure of mice to repeated immobilization sessions (1 hour daily for 7 days) before permanent middle cerebral artery occlusion. Results-We found that TLR4-deficient mice subjected to subacute stress had a better behavioral condition compared with normal mice (C3H/HeN) and that this effect was associated with a minor inflammatory response (cyclooxygenase-2 and inducible nitric oxide synthase expression) and lipid peroxidation (malondialdehyde levels) in brain tissue. Furthermore, previous exposure to stress was followed by a smaller infarct volume after permanent middle cerebral artery occlusion in TLR4-deficient mice than in mice that express TLR4 normally. Conclusions-Our results indicate that TLR4 is involved in the inflammatory response after subacute stress and its exacerbating effect on stroke. These data implicate the effects of innate immunity on inflammation and damage in the brain after stroke.

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Tumor necrosis factor-α: is there a continuum of liability between stress, anxiety states and anorexia nervosa?

Cited by 35 publications

References 67 publications

Levels of Tumour Necrosis Factor-Alpha and Interleukin-6 in Severely Ill Patients with Eating Disorders

Levels of Tumour Necrosis Factor-Alpha and Interleukin-6 in Severely Ill Patients with Eating Disorders

The Increase in TNF-α Levels Is Implicated in NF-κB Activation and Inducible Nitric Oxide Synthase Expression in Brain Cortex after Immobilization Stress

Toll-Like Receptor 4 Is Involved in Subacute Stress–Induced Neuroinflammation and in the Worsening of Experimental Stroke

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