Skip to main content

Table 2 Characteristics of included trials related to cytokines

From: Effects of non-pharmacological interventions on inflammatory biomarker expression in patients with fibromyalgia: a systematic review

Reference Participants Study design Diagnosis of FM Treatment group Control group Study duration Outcomes Findings
Ardiç et al. (2007) [37] N = 31 RCT ACR 1990 Balneotherapy Usual care N/A IL-1α, CRP, PGE2, LTB4, RF, ESR In the balneotherapy group, the levels of serum IL-1α significantly decreased after intervention therapy (p <0.05)
Mean age:    (n = 12) (n = 9)   Two time points
43.5 ± 10.2 years (balneotherapy)    3 weeks 3 weeks   (before and at the end of therapy)
48.8 ± 8.8 years (usual care)    5 days per week Healthy   Serum
43.4 ± 8.2 years (healthy)    20 minutes each (n = 10)   
Gender:       
female only       
Ortega et al. (2009) [28] N = 27 Non-RCT (pilot) ACR Patients Healthy N/A IL-1β, IL-2, IFN-γ, TNF-α, IL-8, IL-6, IL-4, After 4 months of exercise, the levels of circulating serum IL-8 and IFN-γ in FM patients decreased significantly (p <0.001, p <0.05, respectively)
Age range:   (unspecified year) (n = 14) (n = 13)   IL-10, CRP, NA, cortisol
30–60 years (patients)    Pool-aquatic exercise    2 time points
28–55 years (healthy)    4 months    (before and two days after finishing the exercise)
Gender:    3 days per week    
female only    60 minutes each    serum
Wang et al. (2009) [34] N = 100 Non-RCT ACR 1990 Patients (inpatients) Healthy 6 months IL-8 At the beginning of the study, the levels of serum IL-8 in FM patients were significantly higher than the healthy control group (p <0.001)
Mean age:    (n = 20) (n = 80)   4 time points
49.9 ± 6.8 years (patients)    Multidisciplinary therapy    (the beginning of the study, 10 days after At the end of the study (6 months), the levels of serum IL-8 in FM patients decreased significantly compared to the beginning of the study (p <0.05) with a decline to the normal range
48.4 ± 11.1 years (healthy)    3 weeks    treatment, at resignation (21 days), and at 6
Gender:    5 days per week    months follow up)
male 15 %, female 85 % (patients)    8-hour session each    serum
male 45.2 %, female 54.8 % (healthy)        
Bjersing et al. (2012) [26] N = 49 RCT ACR 1990 Nordic walking Active control: Low-intensity walking 30 weeks IL-6, IL-8, IGF-1, IGFBP-3, NGF, There were no significant differences pre- and 15-week post-intervention in the levels of serum IGF-1 and IGFBP-3 between the intervention and active control group
Mean age:    (n = 26) (n = 23)   SP, NPY, MMP-3
52 years (total)    15 weeks 15 weeks   3 time points: serum IGF-1, IGFBP-3 The change in serum free IGF-1 correlated positively with an alteration in CSF SP levels (p <0.1), NPY (p = 0.001) and pain threshold (p <0.1)
Gender:    twice a week twice a week   (baseline, after 15 weeks of exercise, 30
female only    40–45 minutes each 40–45 minutes each   weeks of follow up)  
       Two time points: CSF IL-6, IL-8, NGF, SP,  
       NPY, MMP-3  
       (baseline and after 15 weeks of exercise)  
       serum, CSF  
Ortega et al. (2012) [29] N = 18 Non-RCT ACR 1990 Patients Healthy N/A IL-1β, TNF-α, IL-6, IL-10, CRP After 4 months of exercise, the spontaneous and LPS-induced production of IL-6 in FM patients increased and spontaneous TNF-α decreased compared to their basal state
Age range:    (n = 9) (n = 9)   3 time points
30–60 years (patients)    Pool-aquatic exercise    (before, midway through: 4 months and
28–55 years (healthy)    8 months    at the end of program: 8 months) After 8 months of exercise, the production of IL-1β, TNF-α, IL-6 in FM patients decreased compared to their basal state (both spontaneously and in response to LPS activation), with levels similar to (and even lower than in the case of the spontaneous release of TNF-α) those in the healthy control group
Gender:    twice a week    (samples were collected 2 days after
female only    60 minutes each    finishing the last session of the exercise)
serum
After 8 months of exercise, the spontaneous production of IL-10 decreased and the LPS-induced production of IL-10 increased compared to their basal state, with levels higher than those in the healthy control group
Senna et al. (2012) [30] N = 83 RCT ACR 1990 Dietary weight loss Usual care N/A IL-6, CRP The levels of serum IL-6 in the intervention group were significantly lower than the usual care group after 6 months of intervention (p <0.05), although there were no significant differences between the two groups at baseline.
Mean age:    (n = 41) (n = 42)   two time points
44.8 ± 13.6 years (intervention)    6 months 6 months   (baseline and after 6 months of intervention)
(BMI 32.3 ± 1.4)    1200 kcal/day    serum  
46.3 ± 14.4 years (usual care)    (with 15–20 % of energy intake in the form of protein, 50–55 % in the form of carbo-hydrates, and approximately 30 % in the form of fat divided across three meals)     
(BMI 32.8 ± 1.4)        
Gender:        
male 9.8 %, female 90.2 % (intervention)        
male 9.5 %, female 90.5 % (usual care)        
Bjersing et al. (2013) [27] N = 48 RCT ACR 1990 Nordic walking Active control: low-intensity walking 30 weeks IGF-1, IGFBP3, NGF, adiponectin, leptin, resistin, NPY In lean patients, the levels of total serum IGF-1 increased after 15 weeks of exercise (p <0.05).
Mean age:    (n = 26) (n = 22)  
52.0 years (lean group)    (lean 4, overweight 15, obese 7) (lean 5, overweight 11, obese 6)   3 time points The change in the levels of total serum IGF-1 differed significantly between lean and obese patients (p = 0.01).
(BMI 18.5 to 24.9, n = 9)    15 weeks 15 weeks   (baseline, after 15 weeks of exercise, 30
53.0 years (overweight group)    twice a week twice a week   weeks of follow up)  
(BMI 25 to 29.9, n = 26)    40–45 minutes each 40–45 minutes each   serum, CSF  
51.0 years (obese group)        
(BMI ≥30, n = 13)        
Gender:        
female only        
Bote et al. (2014) [35] N = 20 Non-RCT ACR 1990 Patients Inactive patients N/A IL-8, NA, neutrophils’ function After 4 months of exercise, there were no significant changes between exercised and non-exercised FM patients in the concentration of serum IL-8
Mean age:    (n = 10) (n = 10)   3 time points
53 ± 2 years (patients)    Pool-aquatic exercise    (before, midway through: 4 months and After 8 months of exercise, the concentration of serum IL-8 in exercised FM patients decreased significantly compared to the control group (p <0.05).
50 ± 4 years (inactive patients)    8 months    at the end of program: 8 months)
Gender;    twice a week    (samples were collected 2 days after  
female only (patients)    60 minutes each    finishing the last session of the exercise)  
not described (inactive patients)       serum, plasma  
Menzies et al. (2014) [31] N = 64 RCT ACR 1990 Guided imagery Usual care N/A IFN-γ, TNF-α, IL-1β, IL-2, GM-CSF, There were no statistically significant differences between the intervention and control groups in the levels of pro- and anti-inflammatory cytokines at baseline, 6 weeks or 10 weeks
Mean age:    (n = 30) (n = 34)   IL-12, IL-17, IL-8, MCP-1, MIP-1β, IL-6,
44.5 ± 13.1 years (guided imagery)    10 weeks 10 weeks   IL-7, IL-4, IL-5, IL-10, IL-13, G-CSF, CRP
49.1 ± 12.4 years (usual care)    Use CD tracks at least once a daily    3 time points There was a notable trend in the increase of plasma IL-7 in the intervention group, whereas the control group means remained relatively constant across the study interval
Gender:    For the first 6 weeks, listen to the three    (baseline, week 6, week10)
female only    CD tracks (each one CD in two weeks).    plasma
    For the last 4 weeks, listen to the tracks in any order    
  1. ACR American College of Rheumatology, BMI body mass index, CD compact disc, CRP C-reactive protein, CSF cerebrospinal fluid, ESR erythrocyte sedimentation rate, G-CSF granulocyte-colony stimulating factor, GM-CSF granulocyte macrophage colony-stimulating factor, IFN-γ interferon gamma, IGFBP-3 insulin-like growth factor-binding protein-3, IGF-1 insulin-like growth factor-1, IL interleukin, LPS, lipopolysaccharide, LTB4 leukotriene B4, MCP-1 monocyte chemoattractant protein-1, MIP-1β macrophage inflammatory protein-1 beta, MMP-3 matrix metallopeptidase-3, N/A not available, NGF nerve growth factor, NPY neuropeptide Y, Non-RCT non-randomized controlled trial, PGE2 prostaglandin E2, PRL prolactin, RCT randomized controlled trial, RF rheumatoid factor, SP surfactant protein, TNF-α tumor necrosis factor-alpha