Cytokine-induced sickness behavior

Kelley, Keith W.; Bluthé, Rose Marie; Dantzer, Robert; Zhou, Jian; Shen, Wen Hong; Johnson, Rodney W.; Broussard, Suzanne R.

doi:10.1016/s0889-1591(02)00077-6

Cited by 618 publications

(412 citation statements)

References 53 publications

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“…Inhibition of proinflammatory cytokine expression in the brain, including TNF-a, could be secondary to a peripheral antiinflammatory activity of minocycline, or it could be due to the ability of this tetracycline to downregulate microglial activation, and therefore the increased brain proinflammatory cytokine expression that ultimately mediates the sickness-inducing effects of peripherally administered LPS. [32][33][34] Although the ability of minocycline to inhibit expression of the inducible form of nitric oxide synthase during neuroinflammation is well documented, 20 its ability to block activation of IDO had not yet been tested. IFN-g and TNF-a are the main inducers of IDO activation.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

O’Connor

Lawson²,

André³

et al. 2008

Mol Psychiatry

1,123

992

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Although elevated activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) has been proposed to mediate comorbid depression in inflammatory disorders, its causative role has never been tested. We report that peripheral administration of lipopolysaccharide (LPS) activates IDO and culminates in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in both the forced-swim and tail suspension tests. Blockade of IDO activation either indirectly with the anti-inflammatory tetracycline derivative minocycline, that attenuates LPS-induced expression of proinflammatory cytokines, or directly with the IDO antagonist 1-methyltryptophan (1-MT), prevents development of depressive-like behavior. Both minocycline and 1-MT normalize the kynurenine/tryptophan ratio in the plasma and brain of LPS-treated mice without changing the LPS-induced increase in turnover of brain serotonin. Administration of L-kynurenine, a metabolite of tryptophan that is generated by IDO, to naive mice dose dependently induces depressive-like behavior. These results implicate IDO as a critical molecular mediator of inflammation-induced depressive-like behavior, probably through the catabolism of tryptophan along the kynurenine pathway.

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

O’Connor

Lawson²,

André³

et al. 2008

Mol Psychiatry

1,123

992

View full text Add to dashboard Cite

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“…Like cytokines that serve as growth factors, cachetins and pyrogens induce fatigue and influence symptoms and conditions that contribute to fatigue, including fever, anorexia, cachexia, pain, nausea, dyspnea, anemia, sleep loss, and depression. 19,48,49 The different physiological processes inherent across these three classifications of cytokines imply that fatigue and weakness related to growth factors, weight loss, and fever should be distinguished from other sources of fatigue/weakness whenever possible. For instance, it is common for cancer patients to experience weakness from low-grade fever unrelated to infection that is caused by cancer-related etiology.…”

Section: Sickness Behavior and Cytokine Pathways In Cancermentioning

confidence: 99%

The Relationship of Cancer Symptom Clusters to Depressive Affect in the Initial Phase of Palliative Radiation

Francoeur

2005

Journal of Pain and Symptom Management

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Research on comorbidity across cancer symptoms, including pain, fatigue, and depression, could suggest if crossover effects from symptom-specific interventions are plausible. Secondary analyses were conducted on a survey of 268 cancer patients with recurrent disease from a northeastern U.S. city who were initiating palliative radiation for bone pain. Moderator regression analyses predicted variation in depressive affect that could be attributed to symptom clusters. Patients self-reported difficulty controlling each physical symptom over the past month on a Likert scale and depressive symptoms on a validated depression measure (Center for Epidemiologic Studies-Depression [CES-D]) over the past week on a four-category scale. An index of depressive affect was based on items of negative and positive affect from the CES-D. In predicting depressive affect, synergistic interactions of pain with fever, fatigue, and weight loss suggest separate pathways involving pain. A similar interaction with fever occurs when nausea was tested in place of pain. Further, the interaction between pain and fatigue is similar in form to the interaction between difficulty breathing and fatigue (when sleep is not a problem). Follow-up to the latter interaction reveals: 1) additional moderation by hypertension and palliative radiation to the hip/pelvis; and 2) a similar cluster not involving hypertension when appetite problems and weight loss were tested in place of fatigue. The significance and form of these interactions are remarkably consistent. Similar sickness mechanisms could be generating: 1) pain and nausea during fever; 2) pain and fatigue during weight loss; and 3) pain and breathing difficulty when fatigue is pronounced. Crossover effects from symptom-specific interventions appear promising.

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“…These cascades produce a host of neurobehavioural sequelae that have been termed 'sickness behaviour' (Kelley et al, 2003). Symptoms of sickness behaviour include fever, weakness, malaise, listlessness, and concentration difficulties.…”

Section: Bioimmunotherapymentioning

confidence: 99%

Neuropsychological dysfunction associated with cancer and cancer therapies: a conceptual review of an emerging target

2004

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Cytokine-induced sickness behavior

Cited by 618 publications

References 53 publications

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

The Relationship of Cancer Symptom Clusters to Depressive Affect in the Initial Phase of Palliative Radiation

Neuropsychological dysfunction associated with cancer and cancer therapies: a conceptual review of an emerging target

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