Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans

Vollmer‐Conna, Ute; Fazou, Chrysa; Cameron, Barbara; Li, Hongshou; Brennan, Catherine M.; Luck, Lauretta; Davenport, Tracey A; Wakefield, Denis; Hickie, Ian B.; Lloyd, Andrew R.

doi:10.1017/s0033291704001953

Cited by 175 publications

(118 citation statements)

References 28 publications

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“…However, one of the reasons for our lack of association between depression and telomere length in the older cohort might be our choice of depression assessment. The HADS excludes the physical symptoms of depression, and physical symptoms, such as fatigue, are linked to increased inflammation (50). Inflammation is thought to play a role in telomere attrition as well as increasing with age (51); thus, the absence of physical symptoms from our depression measure might underlie the lack of association with telomere attrition in our older cohort.…”

Section: Discussionmentioning

confidence: 99%

Do Symptoms of Depression Predict Telomere Length? Evidence From the West of Scotland Twenty-07 Study

Phillips

Robertson

Carroll

et al. 2013

Psychosomatic Medicine

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Objective: Psychological factors such as the stress of caregiving are emerging as predictors of telomere length, an index of biological ageing. However, although lifetime major depressive disorder is associated with shorter telomeres, less is known about depression symptoms.Depression and depressive symptoms are associated with a range of morbidities and mortality, but the extent to which they predict biological ageing is unclear. The present study examined participants in the West of Scotland Twenty-07 Study across three age cohorts and four waves of data collection from 1992/93 to 2007/08. Methods: Participants were aged 37, 57, and 76 years old at final data collection. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale at each time point. Telomere length was assessed from 1063 blood samples collected at the final wave in 2007/08 for respondents who also had depression data. Results:Average depression symptoms (β = -.12, p = .047) and their change over time (β = -.12, p = .031) were negatively associated with telomere length, but only in the youngest cohort . Depressive symptoms were not cross-sectionally associated with telomere length in 2007-08 (β = -.03, p = .45).In the youngest cohort only, depressive symptoms assessed in 1995-97 and 2000-04 were associated with shorter telomere length (β = .14, p = .046, and β = .18, p = .012, respectively), but not 1992-93 or 2007-08; associations in the middle and older aged cohorts were non-significant. Conclusions:Depressive symptoms predict shorter telomeres, but only in younger adults.Keywords: ageing; depression; telomeres; cohort study; Abbreviations:AUC Area under the curve CES-D Centre for Epidemiologic Studies Depression Scale DNA Deoxyribonucleic acid EDTA Ethylenediaminetetraacetic acid GDS Geriatric Depression Scale HADS Hospital Anxiety and Depression ScaleAuthor's Pre-print, please cite as: Phillips, A.C., Robertson, T., Carroll, D., Der, G., Shiels, P.G., . Do symptoms of depression predict telomere length? Evidence from the West of Scotland Twenty-07 Study. Psychosomatic Medicine, 75,[288][289][290][291][292][293][294][295][296] http://dx.doi.org/10.1097/PSY.0b013e318289e6b5 3 MDD Major Depressive Disorder NHS National Health Service PBL Peripheral blood leukocyte SE Standard error of the mean T/S ratio Telomere repeat copy number to single copy gene number ratio Author's Pre-print, please cite as: Phillips, A.C., Robertson, T., Carroll, D., Der, G., Shiels, P.G., . Do symptoms of depression predict telomere length? Evidence from the West of Scotland Twenty-07 Study. Psychosomatic Medicine, 75,[288][289][290][291][292][293][294][295][296] http://dx.doi.org/10.1097/PSY.0b013e318289e6b5 4 Depression is a strong predictor of morbidity and mortality (see e.g., (1, 2), even when sociodemographic variables and health behaviours are taken into account. The prevalence of depression is high among individuals with ageing-related physical illnesses (3)(4)(5). Several underlying mechanisms have been proposed including telomer...

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Section: Discussionmentioning

confidence: 99%

Do Symptoms of Depression Predict Telomere Length? Evidence From the West of Scotland Twenty-07 Study

Phillips

Robertson

Carroll

et al. 2013

Psychosomatic Medicine

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“…Peripheral blood mononuclear cells (PBMC) and sera were collected, separated and stored under endotoxin-minimised conditions in aliquots as described previously [9,10,24]. After thawing, PBMC were cultured overnight in medium only (unstimulated cultures), in the presence of lipopolysaccharide (LPS) (10 ng/ml, from Salmonella typhimurium, Sigma, St. Louis, MI, USA), or with mouse-anti-human anti-CD3 and anti-CD28 Dynabeads (Dynal, Norway) as described previously [24].…”

Section: Methodsmentioning

confidence: 99%

“…This hypothesis has arisen given the similarity to manifestations of the acute sickness response to infection which are mediated by the action of pro-inflammatory cytokines on the brain [9,10] and to other chronic fatigue states, including post-infective fatigue syndrome [11,12]. During radiation treatment of cancer, the pro-inflammatory cytokines, interleukin (IL)-6, IL-1, and tumour necrosis factor (TNF)-α, have been shown to be induced in the host response to injury of non-hemopoietic tissues [13].…”

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confidence: 99%

Post-cancer fatigue is not associated with immune activation or altered cytokine production

Cameron

Bennett²,

et al. 2012

Annals of Oncology

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“…Several studies have looked into a role for IL-6 as a mediator of immunological processes in various presentations of Q fever. Unstimulated peripheral blood mononuclear cells (PBMC) from patients with acute Q fever released IL-6, the levels of which correlated with self-reported sickness symptoms (8). Correspondingly, human monocyte-derived macrophages infected by C. burnetii secreted IL-6 (9), indicating that lymphocytes and/or monocytes are involved in the production of IL-6 in patients with acute Q fever.…”

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confidence: 99%

Correlations between Peripheral Blood Coxiella burnetii DNA Load, Interleukin-6 Levels, and C-Reactive Protein Levels in Patients with Acute Q Fever

Kremers

Janssen

Wielders

et al. 2014

Clin Vaccine Immunol

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e From 2007 to 2010, the Netherlands experienced the largest reported Q fever outbreak, with >4,000 notified cases. We showed previously that C-reactive protein is the only traditional infection marker reflecting disease activity in acute Q fever. Interleukin-6 is the principal inducer of C-reactive protein. We questioned whether increased C-reactive protein levels in acute Q fever patients coincide with increased interleukin-6 levels and if these levels correlate with the Coxiella burnetii DNA load in serum. In addition, we studied their correlation with disease severity, expressed by hospital admission and the development of fatigue. Interleukin-6 and C-reactive protein levels were analyzed in sera from 102 patients diagnosed with seronegative PCR-positive acute Q fever. Significant but weak negative correlations were observed between bacterial DNA loads expressed as cycle threshold values and interleukin-6 and C-reactive protein levels, while a significant moderate-strong positive correlation was present between interleukin-6 and C-reactive protein levels. Furthermore, significantly higher interleukin-6 and C-reactive protein levels were observed in hospitalized acute Q fever patients in comparison to those in nonhospitalized patients, while bacterial DNA loads were the same in the two groups. No marker was prognostic for the development of fatigue. In conclusion, the correlation between interleukin-6 and C-reactive protein levels in acute Q fever patients points to an immune activation pathway in which interleukin-6 induces the production of C-reactive protein. Significant differences in interleukin-6 and C-reactive protein levels between hospitalized and nonhospitalized patients despite identical bacterial DNA loads suggest an important role for host factors in disease presentation. Higher interleukin-6 and C-reactive protein levels seem predictive of more severe disease.

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Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans

Cited by 175 publications

References 28 publications

Do Symptoms of Depression Predict Telomere Length? Evidence From the West of Scotland Twenty-07 Study

Do Symptoms of Depression Predict Telomere Length? Evidence From the West of Scotland Twenty-07 Study

Post-cancer fatigue is not associated with immune activation or altered cytokine production

Correlations between Peripheral Blood Coxiella burnetii DNA Load, Interleukin-6 Levels, and C-Reactive Protein Levels in Patients with Acute Q Fever

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