. Author manuscript; available in PMC: 2018 Jul 23.

Published in final edited form as: Mol Psychiatry. 2016 Feb 23;21(12):1696–1709. doi: 10.1038/mp.2016.3

Table 3.

Blood cytokine network alterations in MDD

3a. Blood cytokine network levels in acutely ill patients with MDD versus controls

Cytokine component	N				Mean ES	95% CI	P-value	Heterogeneity		I²	References

	Studies	Pt		Control				χ²	P-value

IFN-γ	2	61		54	−1.45	−1.87 to −1.04	<0.01	1.06	0.30	5.7	^78,79
IL-1β	4	116		112	−0.22	−0.49 to 0.06	0.13	80.87	<0.01	94.0	^78,79,81,84
IL-1RA	2	44		25	0.95	0.42–1.48	<0.01	0.97	0.33	0.0	^82,86
IL-2	3	84		79	−0.09	−0.47 to 0.29	0.64	108.92	<0.01	98.2	^78,79,90
IL-4	2	53		57	−0.83	−1.26 to −0.40	<0.01	40.86	<0.01	97.6	^78,90
IL-6	10	306		216	0.76	0.56–0.95	<0.01	96.09	<0.01	90.6	^{74,75,81,82,84–89}
IL-8
IL-10	4	112		103	0.75	0.46–1.04	<0.01	37.32	<0.01	92.0	^78–80,82
IL-12	4	117		172	0.91	0.64–1.17	<0.01	44.69	<0.01	93.3	^45,78,83,90
IL-17
IL-18
sIL-2 R	5	247		170	0.49	0.29–0.70	<0.01	11.04	0.05	54.7	^{77,81,85,87,88}
sIL-6 R	3	145		68	0.66	0.36–0.96	<0.01	2.68	0.26	25.3	^85,86,88
TGF-β
TNF-α	8	296		281	0.35	0.17–0.53	<0.01	136.00	<0.01	94.1	^{77,78,80,81,84,86,88,90}
sTNF-R1
3b. Changes in blood cytokine network levels following treatment of acutely ill patients with MDD

Cytokine component	N			Mean duration	Mean ES change	95% CI	P-value	Heterogeneity		I²	References

	Studies	Pre	Post					χ²	P-value

IFN-γ	2	54	61	112	0.10	−0.27 to 0.47	0.59	0.58	0.45	0.0	^78,79
IL-1β	4	89	82	74	0.39	0.06–0.72	0.02	54.55	<0.01	92.7	^78,79,81,84
IL-1RA	2	34	34	39	0.10	−0.38 to 0.58	0.70	2.30	0.13	56.5	^82,86
IL-2	3	84	77	93	−0.02	−0.38 to 0.34	0.92	82.08	<0.01	97.6	^78,79,90
IL-4	3	84	77	93	0.59	0.25–0.92	<0.01	38.97	<0.01	94.9	^78,79,90
IL-6	7	116	116	45	−0.36	−0.62 to −0.09	0.01	17.95	0.01	61.0	^{74,81,82,84–87}
IL-8
IL-10	2	54	61	112	−1.03	−1.45 to −0.61	<0.01	30.41	<0.01	96.7	^78,79
IL-12	4	86	86	60	−0.54	−0.86 to −0.23	<0.01	20.67	<0.01	85.5	^45,78,83,90
IL-17
IL-18
sIL-2 R	4	139	139	60	−0.04	−0.28 to 0.19	0.72	3.33	0.50	0.0	^77,81,85,87
sIL-6 R	2	42	42	63	−0.11	0.53–0.32	0.93	0.85	0.36	0.0	^85,87
TGF-β
TNF-α	6	205	205	54	−0.12	−0.32 to 0.08	0.22	45.66	<0.01	84.7	^{76–78,81,84,90}
sTNF-R1
3c. Blood cytokine network alterations in chronically ill patients with MDD versus controls

Cytokine component	N				Mean ES	95% CI	P-value	Heterogeneity		I²	References

	Studies	Pt		Control				χ²	P-value

IFN-γ	4	195		226	−0.03	−0.24 to 0.16	0.82	158.68	<0.01	98.1	^{64,109,112,117}
IL-1β	3	105		157	0.21	−0.04 to 0.47	0.10	17.32	<0.01	88.5	^64,111,112
IL-1RA
IL-2	2	82		82	−0.54	−0.90 to −0.17	<0.01	84.19	<0.01	98.8	^64,117
IL-4	2	82		113	−0.01	−0.30 to 0.28	0.94	4.82	0.03	79.3	^64,112
IL-6	7	205		211	0.39	0.20–0.59	<0.01	31.44	<0.01	77.7	^{64,110,112,115,116,118,119}
IL-8	3	126		137	0.08	−0.16 to 0.32	0.49	15.03	<0.01	80.0	^64,112,116
IL-10	4	138		148	−0.23	−0.546 to 0.01	0.06	34.64	<0.01	88.5	^{64,110,112,116}
IL-12	2	82		113	−0.44	−0.75 to −0.14	<0.01	30.32	<0.01	96.7	^64,112
IL-17
IL-18
sIL-2 R	2	117		80	0.05	−0.20 to 0.30	0.68	10.84	0.01	72.3	^113,118
sIL-6 R	2	66		42	−0.09	−0.43 to 0.26	0.63	0.94	0.63	0.0	^115,116
TGF-β
TNF-α	7	346		351	0.05	−0.10 to 0.19	0.52	75.26	<0.01	86.7	^{64,109,111–114,116,109}
sTNF-R1

Abbreviations: ES, effect size; CI, confidence interval; IFN, interferon; IL, interleukin; IL-1RA, interleukin-2 receptor antagonist; N/A, not available; Pt, patients; sIL, soluble interelukin; TGF, tumor growth factor; TNF, tumor necrosis factor.

Bold and italicized values are statistically significant.