Table 2 Characteristics of included trials related to cytokines

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