Table 1.
Blood cytokine network alterations in schizophrenia
| 1a. Blood cytokine network levels in first-episode psychosis versus controls | |||||||||||
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| Cytokine component | N | Mean ES | 95% CI | P-value | Heterogeneity | I2 | References | ||||
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| Studies | Pt | Control | χ2 | P-value | |||||||
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| IFN-γ | 7 | 452 | 747 | 0.23 | 0.09–0.37 | <0.01 | 37.28 | <0.01 | 83.9 | 25,29–31,39,46,47 | |
| IL-1β | 6 | 333 | 298 | 1.25 | 1.07–1.42 | <0.01 | 78.36 | <0.01 | 93.6 | 31,43,57–60 | |
| IL-1RA | 2 | 194 | 376 | 0.29 | 0.10–0.48 | <0.01 | 1.25 | 0.26 | 20.1 | 24,29 | |
| IL-2 | 5 | 140 | 300 | 0.08 | −0.14 to 0.29 | 0.48 | 29.5 | <0.01 | 86.4 | 31,39,43,47,60 | |
| IL-4 | 4 | 193 | 322 | −0.63 | −0.84 to −0.42 | <0.01 | 74.95 | <0.01 | 96.0 | 25,31,46,47 | |
| IL-6 | 11 | 506 | 577 | 1.16 | 1.03–1.30 | <0.01 | 135.67 | <0.01 | 92.6 | 24,25,30,31,35,41,43,47,48,58,59 | |
| IL-8 | 2 | 49 | 49 | 1.75 | 1.27–2.24 | <0.01 | 12.43 | <0.01 | 92.0 | 31,51 | |
| IL-10 | 4 | 357 | 461 | 0.18 | 0.04–0.31 | 0.01 | 38.52 | <0.01 | 92.2 | 29,31,48,61 | |
| IL-12 | 3 | 258 | 463 | 0.26 | 0.05–0.47 | 0.02 | 69.17 | <0.01 | 97.1 | 28,29,45 | |
| IL-17 | 2 | 157 | 96 | 0.00 | −0.26 to 0.26 | 0.99 | 7.91 | <0.01 | 87.4 | 25,30 | |
| IL-18 | 3 | 335 | 403 | 0.08 | −0.07 to 0.23 | 0.28 | 0.87 | 0.65 | 0.0 | 29,62,63 | |
| sIL-2 R | 3 | 30 | 97 | 1.04 | 0.55–1.52 | <0.01 | 10.18 | <0.01 | 80.3 | 24,37,54 | |
| sIL-6 R | |||||||||||
| TGF-β | 3 | 169 | 298 | 0.58 | 0.36–0.80 | <0.01 | 11.86 | <0.01 | 83.1 | 25,46,47 | |
| TNF-α | 9 | 587 | 842 | 0.31 | 0.22–0.39 | <0.01 | 238.22 | <0.01 | 96.6 | 29,31,35,47,48,57–60 | |
| sTNF-R1 | |||||||||||
| 1b. Blood cytokine network levels in acutely ill patients with schizophrenia versus controls | |||||||||||
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| Cytokine component | N | Mean ES | 95% CI | P-value | Heterogeneity | I2 | References | ||||
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| Studies | Pt | Control | χ2 | P-value | |||||||
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| IFN-γ | 4 | 162 | 266 | 0.35 | 0.13–0.57 | <0.01 | 5.34 | 0.15 | 43.9 | 25,42,47 | |
| IL-1β | 3 | 131 | 151 | 0.28 | 0.04–0.52 | 0.02 | 7.41 | 0.02 | 73.0 | 27,32,43 | |
| IL-1RA | 2 | 32 | 94 | 0.49 | 0.07–0.90 | 0.02 | 8.19 | <0.01 | 87.8 | 40,50 | |
| IL-2 | 2 | 43 | 199 | −0.27 | −0.61 to 0.07 | 0.12 | 14.08 | <0.01 | 92.9 | 43,47 | |
| IL-4 | 5 | 169 | 350 | −0.36 | −0.56 to −0.16 | <0.01 | 50.46 | <0.01 | 92.1 | 25,42,46,47,52 | |
| IL-6 | 9 | 278 | 468 | 0.73 | 0.56–0.90 | <0.01 | 134.19 | <0.01 | 94.0 | 25,33,36,38,42,43,47,49,52 | |
| IL-8 | 2 | 46 | 52 | 0.59 | 0.19–1.00 | <0.01 | 2.06 | 0.15 | 51.4 | 42,52 | |
| IL-10 | 2 | 46 | 52 | −0.57 | 0.98 −0.17 | <0.01 | 3.42 | 0.07 | 70.7 | 42,52 | |
| IL-12 | |||||||||||
| IL-17 | |||||||||||
| IL-18 | |||||||||||
| sIL-2 R | 3 | 58 | 120 | 0.47 | 0.14–0.80 | 0.01 | 4.46 | 0.11 | 55.1 | 32,30,50 | |
| sIL-6 R | |||||||||||
| TGF-β | 6 | 243 | 382 | 0.50 | 0.32–0.68 | <0.01 | 14.21 | 0.01 | 64.8 | 25,32,46,47,49 | |
| TNF-α | 7 | 269 | 449 | 0.22 | 0.05–0.39 | 0.01 | 141.05 | <0.01 | 95.7 | 27,33,40,42,47,49,52 | |
| sTNF-R1 | |||||||||||
| 1c. Blood changes in cytokine network levels following treatment of acutely ill patients with schizophrenia | |||||||||||
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| Cytokine component | N | Mean duration | Mean ES Change | 95% CI | P-value | Heterogeneity | I2 | References | |||
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| Studies | Pre | Post | χ2 | P-value | |||||||
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| IFN-γ | 4 | 265 | 265 | 36 | −0.12 | −0.29 to 0.05 | 0.16 | 1.57 | 0.81 | 0.0 | 26,30,44,47 |
| IL-1β | 4 | 189 | 189 | 75 | −0.29 | −0.49 to −0.09 | <0.01 | 4.90 | 0.18 | 38.7 | 43,44,57,59 |
| IL-1RA | |||||||||||
| IL-2 | 4 | 132 | 132 | 49 | −0.03 | −0.27 to 0.22 | 0.84 | 8.27 | 0.04 | 63.7 | 43,44,47,53 |
| IL-4 | 2 | 186 | 186 | 43 | −0.29 | −0.50 to −0.09 | 0.01 | 0.36 | 0.83 | 0.0 | 26,47 |
| IL-6 | 11 | 521 | 500 | 56 | −0.13 | −0.25 to −0.01 | 0.04 | 20.55 | 0.04 | 46.5 | 26,30,33,36,43,42,47,48,53,59 |
| IL-8 | |||||||||||
| IL-10 | |||||||||||
| IL-12 | 3 | 104 | 104 | 42 | 0.33 | 0.06–0.60 | 0.02 | 3.77 | 0.15 | 46.9 | 28,44,45 |
| IL-17 | 2 | 193 | 193 | 29 | 0.13 | −0.07 to 0.33 | 0.22 | 0.49 | 0.78 | 0.0 | 26,30 |
| IL-18 | |||||||||||
| sIL-2 R | 3 | 90 | 90 | 69 | 0.30 | 0.01 to 0.60 | 0.04 | 2.19 | 0.34 | 8.6 | 51,55,56 |
| sIL-6 R | |||||||||||
| TGF-β | 4 | 286 | 286 | 43 | −0.04 | −0.21 to 0.12 | 0.61 | 22.63 | <0.01 | 82.3 | 26,46,47,49 |
| TNF-α | 6 | 310 | 310 | 73 | 0.02 | −0.14 to 0.18 | 0.84 | 15.53 | 0.01 | 67.8 | 33,47,53,57,59 |
| sTNF-R1 | |||||||||||
| 1d. Blood cytokine network alterations in chronically ill patients with schizophrenia versus controls | |||||||||||
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| Cytokine component | N | Mean ES | 95% CI | P-value | Heterogeneity | I2 | References | ||||
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| Studies | Pt | Control | χ2 | P-value | |||||||
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| IFN-γ | 4 | 198 | 132 | −1.07 | −1.35 to −0.80 | <0.01 | 164.70 | <0.01 | 98.2 | 75,77,80,91 | |
| IL-1β | 4 | 330 | 303 | 0.89 | 0.73–1.05 | <0.01 | 101.94 | <0.01 | 96.1 | 75,78,81,91 | |
| IL-1RA | |||||||||||
| IL-2 | 6 | 193 | 171 | −0.04 | −0.24 to 0.16 | 0.68 | 55.25 | <0.01 | 91.0 | 76,80,84,88,90,91 | |
| IL-4 | 2 | 73 | 46 | −0.04 | −0.42 to 0.34 | 0.83 | 0.87 | 0.35 | 0.0 | 80,91 | |
| IL-6 | 12 | 711 | 674 | 0.27 | 0.17 to 0.38 | <0.01 | 110.59 | <0.01 | 88.2 | 75,78,80,81,83,85–91 | |
| IL-8 | |||||||||||
| IL-10 | 4 | 118 | 126 | −0.03 | −0.24 to 0.18 | 0.81 | 4.06 | 0.40 | 1.4 | 75,80,85,91 | |
| IL-12 | |||||||||||
| IL-17 | |||||||||||
| IL-18 | |||||||||||
| sIL-2 R | 3 | 116 | 135 | 0.32 | 0.40–0.86 | <0.01 | 1.42 | 0.70 | 0.0 | 78–80 | |
| sIL-6 R | |||||||||||
| TGF-β | |||||||||||
| TNF-α | 9 | 508 | 509 | 0.30 | 0.18–0.43 | <0.01 | 46.77 | <0.01 | 80.8 | 75,78,80–83,85,90,91 | |
| sTNF-R1 | |||||||||||
Abbreviations: ES, effect size; CI, confidence interval; IFN, interferon; IL, interleukin; IL-1RA, interleukin-2 receptor antagonist; Pt, patients; sIL, soluble interelukin; TGF, tumor growth factor; TNF, tumor necrosis factorr.
Bold and italicized values are statistically significant.