IL-1β reactivity and the development of severe fatigue after military deployment: a longitudinal study

Journal of Neuroinflammation

Cobi J Heijnen³  Elbert Geuze¹  Eric Vermetten¹  Mirjam Maas³  Karima Amarouchi³  Annemieke Kavelaars²  Mirjam van Zuiden⁴ 

[1]Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands

[2]Integrative Immunology and Behavior Program, University of Illinois Urbana Champaign, 61801, Urbana, IL, USA

[3]Laboratory of Neuroimmunology and Developmental Origins of Disease (NIDOD), University Medical Center Utrecht, KC.03.068.0, P.O. Box 85090, 3508 AB, Utrecht, the Netherlands

[4]Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, 1105 AZ, Amsterdam, the Netherlands

关键词: Interleukin-8;    LPS;    Military;    Reactivity;    Receptor;    Interleukin-1;    Cytokine;    Inflammation;    Stress;    Fatigue;   

Others  :  1160278
DOI  :  10.1186/1742-2094-9-205

 received in 2012-03-30, accepted in 2012-08-09,  发布年份 2012

【 摘 要 】

Background

It has been suggested that pro-inflammatory cytokine signaling to the brain may contribute to severe fatigue. We propose that not only the level of circulating cytokines, but also increased reactivity of target cells to cytokines contributes to the effect of cytokines on behavior. Based on this concept, we assessed the reactivity of peripheral blood cells to IL-1β in vitro as a novel approach to investigate whether severe fatigue is associated with increased pro-inflammatory signaling.

Methods

We included 504 soldiers before deployment to a combat-zone. We examined fatigue severity and the response to in vitro stimulation with IL-1β prior to deployment (T0), and 1 (T1) and 6 months (T2) after deployment. IL-8 production was used as read-out. As a control we determined LPS-induced IL-8 production. The presence of severe fatigue was assessed with the Checklist Individual Strength (CIS-20R). Differences in dose–response and the longitudinal course of IL-1β and LPS-induced IL-8 production and fatigue severity were investigated using repeated measures ANOVA.

Results

At T2, the group who had developed severe fatigue (n = 65) had significantly higher IL-1β-induced IL-8 production than the non-fatigued group (n = 439). This group difference was not present at T0, but developed over time. Longitudinal analysis revealed that in the non-fatigued group, IL-1β-induced IL-8 production decreased over time, while IL-1β-induced IL-8 production in the fatigued group had not decreased. To determine whether the observed group difference was specific for IL-1β reactivity, we also analyzed longitudinal LPS-induced IL-8 production. We did not observe a group difference in LPS-induced IL-8 production.

Conclusions

Collectively, our findings indicate that severe fatigue is associated with a higher reactivity to IL-1β. We propose that assessment of the reactivity of the immune system to IL-1β may represent a promising novel method to investigate the association between behavioral abnormalities and pro-inflammatory cytokine signaling.

【 授权许可】

   
2012 van Zuiden et al.; licensee BioMed Central Ltd.

【 图 表 】

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