Elsevier

Cytokine

Volume 84, August 2016, Pages 25-28
Cytokine

Short communication
Evaluation of cytokines, oxidative stress markers and brain-derived neurotrophic factor in patients with fibromyalgia – A controlled cross-sectional study

https://doi.org/10.1016/j.cyto.2016.05.011Get rights and content

Highlights

  • The IL-6, IL-8, TNF-α, TBARS, protein carbonyl and BDNF did not differ between FM patients and controls.

  • The IL-10 levels were higher in FM patients (adjusted p = 0.041).

  • Among FM patients, there was no correlation of depression and disease impact scores with any biomarker tested here.

Abstract

Objectives

Previous studies measuring serum levels of biomarkers of inflammation/oxidative stress and neurotrophins levels in fibromyalgia (FM) have rendered inconsistent results. In the present study, our aim was to explore the levels of interleukins, oxidative stress markers and brain-derived neurotrophic factor (BDNF) in patients with FM in relation to depression and severity of disease.

Methods

In a prospective controlled cross-sectional study, serum concentrations of IL-6, IL-8, IL-10, TNF-α, thiobarbituric acid reactive substances (TBARS), protein carbonyl and BDNF were measured in 69 FM patients and 61 healthy controls (all women). In the FM group, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS) were applied. Mann Whitney’s and Spearman correlation tests were used for statistical analysis.

Results

The FM patients demonstrated a significant impact of the disease on quality of life (FIQ 70.2 ± 17.8) and most of them had depression at some level (82.6% and 87.0% as assessed by BDI and HDRS, respectively). Most biomarkers (IL-6, IL-8, TNF-α, TBARS and protein carbonyl) and BDNF did not differ significantly between patients and controls, but the IL-10 levels were higher in FM patients (adjusted p = 0.041). Among FM patients, there was no correlation of HDRS, FIQ, and BDI scores with any biomarker tested here.

Conclusion

We observed no significant differences in biomarkers between FM patients and controls, except for higher levels of IL-10 (an anti-inflammatory cytokine) in patients. The levels of biomarkers were not correlated with parameters of disease and depression severity.

Introduction

Fibromyalgia (FM) is a common disease with a complex and not completely known pathophysiology. Along with generalized pain, depression is frequently present in the disease context, which a prevalence ranging from 28.6% to 70% [1].

There are no reliable laboratory markers of disease activity or severity in FM. Studies evaluating levels of interleukins (IL), including IL-6, IL-8, IL-10, IL-4, and IL-2, as well as tumor necrosis factor (TNF-α) in FM, have rendered inconsistent results [2], [3], [4], [5], [6]. Higher levels of brain-derived neurotrophic factor (BDNF) was found in blood and cerebrospinal fluid (CSF) of FM patients [7], [8], [9]. There is also evidence of increased levels of biomarkers of oxidative stress (like protein carbonyl content and Thiobarbituric Acid Reactive Substances (TBARS) in FM [10], [11]. However, it is possible that the interplay between biomarkers is more important than their isolated levels in certain diseases. In view of that, Kapczinski and colleagues developed a multi-biomarker score for mood disorders called Systemic Toxicity Index (STI), which differentiated patients with mania or depression from healthy control subjects [12]. The STI has not been studied in patients with FM so far.

Our aim in this study is to investigate the serum concentrations of cytokines (IL-6, IL-8, IL-10 and TNF-α), BDNF and stress oxidative biomarkers (carbonyl and TBARS), as wells as their interconnection using the STI, in patients with FM in comparison to healthy controls. We also test the possibility of association of the biomarkers with the severity of FM and depression in these patients.

Section snippets

Study design and participants

A prospective controlled cross-sectional study was conducted at the Rheumatology Departments of the Hospital das Clínicas da Universidade Federal de Pernambuco (HC/UFPE) and Hospital de Clínicas de Porto Alegre (HCPA). Subjects’ recruitment and data collection occurred between Sep/2011 and Nov/2012.

The patients were consecutively selected from the outpatient clinic specialized in the care of fibromyalgia patients at the HC/UFPE. All subjects fulfilled both the American College of Rheumatology

Results

We recruited 69 FM patients and 61 controls (all female). Age was similar between groups (44.5 ± 6.4 years in FM and 44.0 ± 6.7 in controls). The clinical data of FM patients are described in Table 1. The FM patient had in general long disease duration, almost half were using antidepressant drugs (in doses for treatment of depression) and the overall impact of FM on quality of life, measured by FIQ, was high (70.2 ± 17.8). Most FM patients had at least some level of depression (82.5% by BDI and 87.0%

Discussion

Fibromyalgia is a complex and heterogeneous condition characterized by a disorder in pain processing associated with other defined secondary symptoms and poor quality of life [16]. The prevalence of mood disturbance in FM is about three times higher than in the general population [1]. Mood disturbance has been related to altered levels of some biomarkers. Two meta-analysis showed significantly higher levels of IL-6 and TNF-α in patients with major depression [17], [18]. Substances linked to an

Conclusion

Our results do not support that the levels of cytokines (except perhaps for IL-10), markers of oxidative stress and BDNF are higher in FM patients, and we did not find correlations between depression and the biomarkers in these patients. Additional studies and better standardization of research methods is still needed in this field.

Funding

This work was supported in part by grants from Fundo de Incentivo à Pesquisa e Eventos (FIPE) of Hospital de Clínicas de Porto Alegre (HCPA). The funder was not involved in writing, study design, collection, analysis or interpretation of data.

Conflict of interest statement

The authors declare no conflicts of interest.

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