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Kim, Park, Won, Choi, Kim, Chun, Yoon, Kim, and Kim: Correlation between serum cytokines and clinical feature of children with mild lower respiratory infection

Abstract

Purpose

Acute lower respiratory infection (ALRI), which is frequently encountered in pediatric patients, is the leading cause of hospitalization. We aimed to identify particular cytokines that correlated with ALRI clinical characteristics. We also aimed to identify any differences in cytokines between respiratory syncytial virus (RSV)-related ALRI and non-RSV-related ALRI.

Methods

Cytokine levels were measured in the sera sampled from 103 pediatric patients diagnosed with ALRI and admitted to Seoul St. Mary's Hospital between May 2012 and April 2013. The correlations between cytokine levels and the length of hospitalization, the number of days with fever, body temperature, pulse rate, respiration rate, oxygen saturation upon admission, and duration of oxygen supplementation were analyzed.

Results

In children with ALRI, the level of interleukin (IL)-6, granulocyte-colony stimulating factor (G-CSF), and IL-10 were correlated with a higher body temperature on admission. In addition, the IL-8 level was correlated with pulse rate and respiration rate, and IL-1β level was related with oxygen saturation on admission. In children with RSV-related ALRI, the IL-6 was correlated the with duration of fever, and the IL-1β, IL-2, and IL-8 levels were related to pulse rate and respiration rate. In addition, the increase in interferon-gamma-inducible protein-10 (IP-10) level was correlated with a higher body temperature on admission and a longer duration of hospitalization in children with RSV-related ALRI.

Conclusion

In children with ALRI, the levels of IL-6, IL-8, IL-1β, G-CSF, and IP-10 were correlated with its clinical features. In children with RSV-related ALRI, the IL-1β, IL-2, IL-6, IL-8, and IP-10 level was correlated with the severity of the disease.

Figures and Tables

Table 1

Demographic and clinical characteristics of patients (n=103)

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Characteristic Value
Sex
 Male 59 (57.3)
 Female 44 (42.7)
Age (yr) 1.9 ± 2.8
Length of hospital stay (day) 4.7 ± 1.8
Duration of fever before admission (day) 2.4 ± 2.2
Duration of fever after admission (day) 1.1 ± 1.0
Total duration of fever (day) 3.5 ± 2.7
Type of ALRI
 Acute bronchitis 5 (4.9)
 Pneumonia 69 (67.0)
 Acute bronchiolitis 29 (28.2)
Allergic history
 Allergic rhinitis 2 (1.9)
 Atopic dermatitis 2 (1.9)
 Asthma 1 (1.0)
Clinical symptom
 Cough
  No 0 (0)
  Yes 103 (100)
 Productive cough
  No 11 (10.7)
  Yes 92 (89.3)
 Rhinorrhea
  No 17 (16.5)
  Yes 86 (83.5)
 Previous admission history due to LRTIs (n = 102)
  No 74 (72.6)
  Yes 28 (27.4)
 Pneumococcus vaccination (n = 99)
  No 10 (10.1)
  Yes 89 (89.9)

Values are presented as number (%) or mean±standard deviation.

ALRI, Acute lower respiratory infection; LRTI, lower respiratory tract infection.

Table 2

Correlation between cytokines and clinical manifestations (n=103)

aard-5-99-i002
Cytokine Length of hospitalization Duration of fever before admission Duration of fever after admission Total duration of fever Body temperature Pulse rate Respiratory rate Initial O2 saturation (n = 11) Duration of O2 supplementation
IL-1β −0.02 (0.81) −0.02 (0.87) −0.05 (0.63) −0.02 (0.81) 0.04 (0.69) 0.01 (0.42) 0.02 (0.66) 0.38 (0.04)* 0.18 (0.20)
IL-2 −0.09 (0.37) 0.03 (0.79) −0.03 (0.98) 0.04 (0.69) −0.01 (0.96) 0.00 (0.55) 0.02 (0.21) 0.09 (0.33) 0.20 (0.16)
IL-6 0.08 (0.41) 0.10 (0.29) 0.19 (0.05) 0.17 (0.09) 0.24 (0.01)* < 0.01 (0.84) 0.08 (0.37) 0.22 (0.15) 0.09 (0.38)
IL-8 0.02 (0.86) −0.09 (0.35) −0.10 (0.33) −0.07 (0.45) 0.03 (0.79) 0.05 (0.03)* 0.05 (0.02)* 0.01 (0.80) 0.00 (0.90)
G-CSF 0.02 (0.85) 0.07 (0.48) 0.05 (0.59) 0.07 (0.48) 0.23 (0.02)* 0.03 (0.08) 0.07 (0.42) 0.25 (0.12) 0.16 (0.22)
IFN-γ −0.19 (0.05) 0.01 (0.99) −0.02 (0.82) −0.03 (0.79) 0.02 (0.86) 0.03 (0.24) 0.02 (0.71) 0.18 (0.20) 0.04 (0.54)
IP-10 0.05 (0.59) 0.10 (0.56) 0.16 (0.10) 0.11 (0.28) 0.35 (0.00)* 0.03 (0.61) 0.01 (0.30) 0.01 (0.73) 0.00 (0.89)
TNF-α −0.20 (0.12) −0.0 (0.67) −0.09 (0.38) −0.09 (0.39) −0.09 (0.39) < 0.01 (0.81) 0.04 (0.60) 0.07 (0.42) 0.02 (0.70)

Values are presented as spearman correlation coefficient (P-value). Eleven of patients are checked initial O2 saturation.

IL, interleukin; G-CSF, granulocyte-colony stimulating factor; IFN, interferon; IP-10, interferon-gamma-inducible protein-10; TNF, tumor necrosis factor.

*P<0.05.

Table 3

Correlation between cytokines and clinical manifestations in virus other than RSV infection (n=59)

aard-5-99-i003
Cytokine Length of hospitalization Duration of fever before admission Duration of fever after admission Total duration of fever Body temperature Pulse rate Respiratory rate Initial O2 saturation (n = 7) Duration of O2 supplementation
IL-1β −0.03 (0.83) −0.12 (0.35) −0.17 (0.20) −0.14 (0.30) 0.07 (0.61) 0.01 (0.45) 0.07 (0.52) 0.05 (0.64) 0.02 (0.75)
IL-2 −0.26 (0.04*) −0.04 (0.77) −0.17 (0.20) −0.06 (0.66) −0.10 (0.45) < 0.01 (0.97) 0.01 (0.38) 0.25 (0.25) 0.48 (0.09)
IL-6 0.07 (0.59) 0.08 (0.55) 0.07 (0.58) 0.12 (0.37) 0.27 (0.04)* < 0.01 (0.93) 0.01 (0.44) 0.32 (0.19) 0.06 (0.60)
IL-8 −0.04 (0.77) −0.20 (0.13) −0.23 (0.08) −0.22 (0.09) 0.06 (0.64) 0.02 (0.28) 0.02 (0.36) 0.39 (0.13) 0.01(0.96)
G-CSF −0.03 (0.80) 0.11 (0.41) 0.05 (0.71) 0.09 (0.50) 0.27 (0.04)* 0.05 (0.10) 0.01 (0.49) 0.01 (0.86) 0.02 (0.77)
IFN-γ −0.23 (0.08) −0.10 (0.45) −0.08 (0.56) −0.11 (0.41) 0.01 (0.94) 0.01 (0.84) 0.01 (0.47) 0.00 (0.91) 0.02 (0.78)
IP-10 −0.10 (0.45) 0.08 (0.54) 0.18 (0.17) 0.11 (0.40) 0.38 (0.00)* 0.02 (0.76) 0.01 (0.37) 0.06 (0.61) 0.01 (0.81)
TNF-α −0.23 (0.09) −0.03 (0.81) −0.03 (0.80) −0.01 (0.92) −0.00 (0.99) 0.01 (0.86) 0.00 (0.65) 0.00 (0.94) 0.02 (0.75)

Values are presented as spearman correlation coefficient (P-value). Seven of patients affected virus other than RSV are checked initial O2 saturation.

RSV, respiratory syncytial virus; IL, interleukin; G-CSF, granulocyte-colony stimulating factor; IFN, interferon; IP-10, interferon-gamma-inducible protein-10; TNF, tumor necrosis factor.

*P<0.05.

Table 4

Correlation between cytokines and clinical manifestations (RSV infection: n=44)

aard-5-99-i004
Cytokine Length of hospitalization Duration of fever before admission Duration of fever after admission Total duration of fever Body temperature Pulse rate Respiratory rate Initial O2 saturation (n = 4) Duration of O2 supplementation (n = 4)
IL-1β −0.01 (0.93) 0.11 (0.47) 0.12 (0.44) 0.11 (0.46) −0.01 (0.97) 0.16 (0.01)* 0.13 (0.02)* 0.29 (0.46) 0.02 (0.85)
IL-2 0.19 (0.22) 0.11 (0.49) 0.21 (0.18) 0.17 (0.26) 0.18 (0.24) 0.26 (0.01*) 0.16 (0.01*) 0.03 (0.83) 0.04 (0.81)
IL-6 0.12 (0.43) 0.18 (0.23) 0.34 (0.02)* 0.27 (0.08) 0.21 (0.18) 0.05 (0.13) 0.05 (0.14) 0.05 (0.78) 0.00 (0.94)
IL-8 0.11 (0.49) 0.09 (0.55) 0.12 (0.44) 0.16 (0.29) 0.02 (0.89) 0.20 (0.01)* 0.22 (0.01)* 0.24 (0.51) 0.58 (0.24)
G-CSF 0.16 (0.30) 0.02 (0.89) 0.11 (0.49) 0.06 (0.70) 0.19 (0.22) 0.03 (0.23) 0.03 (0.74) 0.27 (0.48) 0.35 (0.41)
IFN-γ −0.10 (0.50) 0.13 (0.39) 0.09 (0.54) 0.09 (0.56) 0.05 (0.77) 0.06 (0.13) 0.02 (0.77) 0.13 (0.64) 0.02 (0.85)
IP-10 0.33 (0.03)* 0.04 (0.82) 0.17 (0.28) 0.13 (0.39) 0.35 (0.02)* 0.05 (0.16) 0.01 (0.89) 0.08 (0.71) 0.12 (0.65)
TNF-α −0.07 (0.66) −0.07 (0.64) −0.14 (0.38) −0.18 (0.23) −0.16 (0.29) 0.01 (0.91) 0.02 (0.78) 0.01 (0.98) 0.36 (0.40)

Values are presented as spearman correlation coefficient (P-value). Four of patients affected RSV virus are checked initial O2 saturation.

RSV, respiratory syncytial virus; IL, interleukin; G-CSF, granulocyte-colony stimulating factor; IFN, interferon; IP-10, interferon-gamma-inducible protein-10; TNF, tumor necrosis factor.

*P<0.05.

Table 5

Acute lower respiratory tract infection pathogens (n=103)

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Pathogen No. of positive cases (%)
Respiratory syncytial virus 44 (42.7)
Parainfluenza virus 9 (8.7)
Adenovirus 8 (7.8)
Bocavirus 7 (6.8)
Pneumococcus 7 (6.8)
Rhinovirus 7 (6.8)
Mycoplasma pneumoniae 7 (6.8)
Metapneumovirus 6 (5.8)
Influenzavirus A 2 (1.9)
Influenzavirus B 1 (0.9)
Coronavirus 1 (0.9)
Total* 84 (81.6)

*Multiple pathogens infecting the same patient was counted as one case.

Table 6

Correlation between cytokines and number of pathogens

aard-5-99-i006
Cytokine No pathogen (n = 20) Single pathogen (n = 71) Multiple pathogen (n = 12) P-value
IL-1β (ng/mL) 243.5 ± 818.4 37.1 ± 147.8 11.9 ± 19.4 0.086
IL-2 (ng/mL) 35.6 ± 48.6 28.1 ± 44.5 32.9 ± 31.5 0.778
IL-6 (ng/mL) 1,457.0 ± 4,311.7 2,139.2 ± 1,6562.1 50.8 ± 58.0 0.887
IL-8 (ng/mL) 6,026.5 ± 9,509.8 3,897.4 ± 1,2442.1 637.2 ± 1,383.9 0.423
G-CSF (ng/mL) 93.7 ± 152.1 93.5 ± 235.0 82.7 ± 114.0 0.986
IFN-γ (ng/mL) 117.5 ± 207.9 80.6 ± 131.7 172.6 ± 369.4 0.262
IP-10 (ng/mL) 6,494.2 ± 14,712.8 3,302.2 ± 3,336.3 2,641.7 ± 2,458.0 0.170
TNF-α (ng/mL) 113.3 ± 162.9 80.9 ± 163.0 8,149.5 ± 2,7507.3 0.019*

Values are presented as mean±standard deviation.

IL, interleukin; G-CSF, granulocyte-colony stimulating factor; IFN, interferon; IP-10, interferon-gamma-inducible protein-10; TNF, tumor necrosis factor.

*P<0.05 between single pathogen and multiple pathogen after Bonferroni post hoc analysis.

Notes

The statistical consultation was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C1731).

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Seung Jun Choi
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