Table 1.
The association between cytokines, chemokines, and EV71-infected HFMD.
| Cytokines/chemokines (sources) | Countries/regions | Study type | Sample type | Complications/severe cases | OR/ROC | Level/value | Progression | p value | Study (year) |
|---|---|---|---|---|---|---|---|---|---|
| TNF-α (Mφ) | China-Zhengzhou | Case-control | Serum | Fatal cases (n = 50): BE+NPE+sepsis | 4.325 | Peak value Declined |
The 2nd day 3-5 days |
0.003 < 0.001 | Duan et al. (2014) [10] |
| China-Shandong | Case-control | Serum | NPE (n = 37), CNSF (n = 29) | 4.593 | Elevated | The 3rd day | 0.001 | Sun et al. (2018) [12] | |
| China-Zhejiang | Case-control | Serum | Severe (n = 40): AFP, convulsions Critical (n = 12): coma, dyspnea, PE |
— | Elevated | Hospitalized | <0.01 | Zheng et al. (2017) [11] | |
|
| |||||||||
| IFN-γ (Th1) | China-Zhengzhou | Case-control | Serum | Fatal cases (n = 50): BE+NPE+sepsis | 4.325 | Low High |
The 2nd day 3-5days |
0.017 <0.017 |
Duan et al. (2014) [10] |
| China-Shandong | Case-control | Serum | NPE (n = 37) CNSF (n = 29) |
4.593 | Elevated Declined |
The 1st day The 3rd day |
<0.01 | Sun et al. (2018) [12] | |
| China-Qingdao | Case-control | Blood | Encephalitis (n = 65) | 2.04 | (A allele) Elevated |
— | <0.01 | Yang et al. (2012) [15] | |
| Taiwan | Case-control | Plasma | ANSD (n = 25), PE (n = 14), BE (n = 34) | — | Elevated | — | 0.048 | Wang et al. (2003) [17] | |
|
| |||||||||
| IL-1β (Mφ) | Malaysian | Case-control | Serum, CSF | AM (n = 8), E (n = 21), AFP (n = 1), CRC (n = 11) | — | Elevated | Hospitalized | 0.013 | Griffiths et al. (2012) [14] |
| China-Nanjing | Case-control | Plasma, CSF | Severe (n = 25): myoclonus, ataxia Critical (n = 12): coma, RF, CC |
2.168 | Elevated Declined |
Acute stage Convalescence |
<0.05 <0.05 |
Ye et al. (2015) [20] | |
|
| |||||||||
| IL-6 (Th2, Mφ) | Taiwan | Case-control | CSF, serum | E (12), PLS (3), AM (7), PE (8) | — | Elevated | The 2nd day | <0.001 | Lin et al. (2003) [33] |
| China-Zhengzhou | Case-control | Serum | Fatal cases (n = 50): BE+NPE+sepsis | 4.325 | Elevated Declined |
2-3 days 4-5 days |
0.003 <0.001 |
Duan et al. (2014) [10] | |
| China-Zhejiang | Case-control | Serum | Severe (n = 40): AFP, convulsions Critical (n = 12): coma, dyspnea, PE |
— | Elevated Declined |
Hospitalized convalescence | <0.01 <0.01 |
Zheng et al. (2017) [11] | |
| China-Guangdong | Case-control | Serum | Stages II (n = 30), III (n = 30), IV (n = 22) | — | Elevated | TP0 | <0.01 | Chen et al. (2014) [31] | |
| China-Qingdao | Case-control | CSF, serum | Encephalitis (n = 59) | 3.31 | (G allele) Elevated |
— | <0.001 | Yuan et al. (2015) [34] | |
| Korea, Seoul | Case-control | Serum | Aseptic meningitis (n = 54) | 7.44/AUC = 0.95 | Elevated | — | <0.001 | Lee et al. (2018) [35] | |
|
| |||||||||
| IL-8 (Mφ) | China-Shandong | Case-control | Plasma | Severe (n = 80): E (36) + CNSF + RF+ dysaemia | 1.8 | (T allele) Elevated |
— | 0.012 | Xu et al. (2016) [37] |
| China-Nanjing | Case-control | Plasma | Severe (n = 25): myoclonus, ataxia Critical (n = 12): coma, RF, CC |
2.168 | Elevated Declined |
Acute stage Convalescence |
<0.05 <0.05 |
Ye et al. (2015) [20] | |
| China-Shenzhen | Case-control | Serum | Severe (n = 41): CNSF+CRC Critical (n = 34): convulsions+coma +BH+dyspnea |
AUC = 0.46 | Elevated | — | <0.001 | He et al. (2019) [38] | |
| Beijing | Case-control | Serum | Mild (n = 32): CNSF, RF Severe (n = 59): PE (8), GT (16), MI (4), death (4) |
— | Peak value Peak value |
The 6th day The 11th day |
<0.001 | Han et al. (2014) [22] | |
| Beijing | Case-control | Serum | BE (n = 47) PE (n = 12) BE+PE (n = 25) |
5.833 | Peak value Declined |
The 1st day The 4th day |
NS NS 0.002 |
Wang et al. (2014) [39] | |
|
| |||||||||
| IL-4 (Th2) | China-Zhengzhou | Case-control | Serum | Fatal cases (n = 50): BE+NPE+sepsis | 4.325 | Elevated | 2-4 days | 0.001 | Duan et al. (2014) [10] |
| China | Case-control | Serum | Viral encephalitis (n = 24) | 15.721 | Elevated | — | <0.001 | Zhang et al. (2015) [29] | |
| Beijing | Case-control | Serum | Mild (n = 32): CNSF, RF Severe (n = 59): PE (8), GT (16), MI (4), death (4) |
— | Higher Higher |
2-6 days 7-14 days |
<0.001 | Han et al. (2014) [22] | |
|
| |||||||||
| IL-10 (Th2, Mφ) | Taiwan | Case-control | Plasma | ANSD (n = 25), PE (n = 14), BE (n = 34) | — | Elevated | — | <0.001 | Wang et al. (2003) [17] |
| China-Shandong | Case-control | Serum | NPE (n = 37) CNSD (n = 29) |
4.593 | Elevated Declined |
The 3rd day The 5th day |
0.001 <0.05 |
Sun et al. (2018) [12] | |
| China-Qingdao | Case-control | Plasma | Severe (n = 70): vomiting, convulsion Critical (n = 17): coma, CRC, PE, CC |
2.998 | (C allele) Elevated |
— | <0.01 | Zhao et al. (2017) [40] | |
| China-Guangdong | Case-control | Serum | Stages II (n = 30), III (n = 30), IV (n = 22) | — | Elevated | TP0 | <0.01 | Chen et al. (2014) [31] | |
| China-Qingdao | Case-control | Blood | Encephalitis (n = 65) | 1.86 | (A allele) Elevated |
— | <0.05 | Yang et al. (2012) [15] | |
|
| |||||||||
| IL-12 (Th1) | China-Hangzhou | Case-control | Plasma | Mild (n = 11): typical symptom Severe cases (n = 28): E (17), E+PE (11) |
— | Elevated | Within 24 h | <0.01 | Shang et al. (2017) [16] |
|
| |||||||||
| IL-13 (Th2) | Taiwan | Case-control | Plasma | ANSD (n = 25), PE (n = 14), BE (n = 34) | — | Elevated | — | 0.048 | Wang et al. (2003) [17] |
| China-Guangdong | Case-control | Serum | Stages II (n = 30), III (n = 30), IV (n = 22) | — | Elevated | TP0 | <0.01 | Chen et al. (2014) [31] | |
| China-Dongying | Case-control | Serum | Severe (n = 162): vomiting, AFP, convulsions, etc. | 0.969 | (G allele) NS |
— | >0.05 | Zhang et al. (2019) [32] | |
|
| |||||||||
| IL-17F (Th17) | China-Qingdao | Case-control | Blood | Encephalitis (n = 58) | 0.31 | (C allele) Declined |
— | 0.006 | Lv et al. (2013) [41] |
| China-Qingdao | Case-control | Blood | Severe (n = 115): typical symptom encephalitis (n = 72) | 1.916 | (T allele) Elevated |
— | 0.001 | Li et al. (2018) [42] | |
|
| |||||||||
| IL-18 (Th1) | Beijing | Case-control | Serum | Mild (n = 32): CNSF, RF Severe (n = 59): PE (8), GT (16), MI (4), death (4) |
— | Peak value Peak value |
The 3th day The 11th day |
<0.001 | Han et al. (2014) [22] |
|
| |||||||||
| IL-22 (Th17, Th22) | China | Case-control | Serum | Viral encephalitis (n = 24) | 8.28 | Elevated | — | 0.026 | Zhang et al. (2015) [29] |
| China-Zhejiang | Case-control | Plasma | Mild (n = 32): typical symptom Severe (n = 24): CRC, BH, MI, etc. |
— | Elevated | — | <0.01 <0.001 |
Cui et al. (2017) [43] | |
|
| |||||||||
| IL-23 (DC, Mφ) | China | Case-control | Serum | Viral encephalitis (n = 24) | 4.564 | Elevated | — | 0.002 | Zhang et al. (2015) [29] |
|
| |||||||||
| IL-33 (DC, Mφ) | Shenzhen | Case-control | Plasma | Severe (n = 23): myoclonus, vomiting Critical (n = 8): acute RF, PE |
2.348 | Elevated | Hospitalized | <0.01 | Zhang et al. (2013) [24] |
|
| |||||||||
| IL-27 (APC) | China-Guangzhou | Case-control | Serum | Stages II (n = 55), III (n = 42), IV (n = 30) | — | — Elevated Declined |
TP0 TP1 TP2 |
— <0.05 <0.01 |
Huang et al. (2016) [44] |
|
| |||||||||
| IL-35 (Treg) | China-Henan | Case-control | Serum | Mild (n = 30): typical symptom Severe (n = 17): CNSF, CRC |
— | Declined | — | <0.0001 | Huang et al. (2017) [45] |
|
| |||||||||
| IL-37 (APC) | China-Hefei | Case-control | Blood | Patients (n = 60): typical symptom | — | Elevated | — | <0.05 | Lv et al. (2019) [27] |
|
| |||||||||
| IP-10 (Mφ) | Shenzhen | Case-control | Plasma | Severe (n = 23): myoclonus, vomiting Critical (n = 8): acute RF, PE |
2.348 | Elevated | Hospitalized | <0.01 | Zhang et al. (2013) [24] |
| China-Qingdao | Case-control | Blood | Patients (n = 58): typical symptom | 0.35 | (T allele) Declined |
— | <0.05 | Yang et al. (2013) [46] | |
|
| |||||||||
| MCP-1 (Mφ) | China-Hangzhou | Case-control | Plasma | Mild (n = 11): typical symptom Severe cases (n = 28): E (17), E + PE (11) |
— | Elevated | Within 24 h | <0.01 | Shang et al. (2017) [16] |
| Shenzhen | Case-control | Plasma | Acute RF (n = 8) | 2.348 | Elevated | Hospitalized | <0.01 | Zhang et al. (2013) [24] | |
|
| |||||||||
| RANTES (NK, CD8+) | China-Hangzhou | Case-control | Plasma | Mild (n = 11): typical symptom Severe cases (n = 28): E (17), E + PE (11) |
— | Elevated | Within 24 h | <0.01 | Shang et al. (2017) [16] |
|
| |||||||||
| HMGB1 (Mφ) | China-Zhejiang | Case-control | Serum | Severe (n = 40): AFP, convulsions Critical (n = 12): coma, dyspnea, PE |
— | Elevated Declined |
Hospitalized recovered | <0.01 <0.01 |
Zheng et al. (2017) [11] |
|
| |||||||||
| G-CSF (EC, FB) | Malaysian | Case-control | CSF | AM (n = 8), E (n = 21), AFP (n = 1), CRC (n = 11) | — | Elevated | Hospitalized | <0.01 | Griffiths et al. (2012) [14] |
Mφ: monocytes/macrophages; Th: helper T lymphocytes; DC: dendritic cells; APC: antigen-presenting cells; Treg cells: regulatory T cells; NK: natural killer cell; EC: endothelial cells; FB: fibroblasts; E: encephalitis; AM: aseptic meningitis; AFP: acute flaccid paralysis; NPE: neurogenic pulmonary edema; CNSF: central nervous system failure; CSF: cerebrospinal fluid; PLS: poliomyelitis-like syndrome; BE: brainstem encephalitis; PE: pulmonary edema; CRC: cardiorespiratory complication; RF: respiratory failure; CC: circulatory collapse; BH: brain hernia; GT: gastrointestinal symptoms; MI: myocardial injury; ANSD: autonomic nervous system dysregulation; AUC: area under the curve; IP-10: interferon-induced protein 10; MCP-1: monocyte chemoattractant protein-1; HMGB1: high mobility group protein 1; G-CSF: granulocyte colony-stimulating factor. Stage II means involvement of the nervous system; stage III means early cardiopulmonary failure; and stage IV means cardiopulmonary failure. TP0 means the day of admission; TP1 means the day the disease improved; and TP3 means the day the disease recovered.