. 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 2.

Blood cytokine network alterations in bipolar disorder

2a. Blood cytokine network levels in acute ill patients with bipolar mania versus controls

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

	Studies	Pt		Control				χ²	P-value

IFN-γ
IL-1β
IL-1RA	2	46		53	0.83	0.42–1.25	<0.01	0.05	0.82	0.0	^67,73
IL-2
IL-4
IL-6	2	44		160	0.59	0.25–0.93	<0.01	3.49	0.06	71.4	^64,68
IL-8
IL-10	2	61		116	0.18	−0.11 to 0.47	0.22	1.21	0.55	0.0	^64,66
IL-12
IL-17
IL-18
sIL-2 R	3	82		90	0.66	0.35–0.97	<0.01	1.81	0.41	0.0	^70–72
sIL-6 R	3	82		90	0.17	−0.13 to 0.48	0.26	0.04	0.98	0.0	^70–72
TGF-β
TNF-α	3	73		137	0.43	0.12–0.74	<0.01	12.68	<0.01	84.2	^64,66,68
sTNF-R1
2b. Changes in blood cytokine network levels following treatment of acutely ill bipolar mania

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

	Studies	Pre	Post					χ²	P-value

IFN-γ
IL-1β	2	46	62	N/A	−0.46	−0.86 to −0.07	0.02	0.22	0.64	0.0	^67,73
IL-1RA
IL-2
IL-4
IL-6
IL-8
IL-10
IL-12
IL-17
IL-18
sIL-2 R	3	82	82	N/A	−0.27	−0.58 to 0.03	0.08	0.12	0.94	0.0	^70–72
sIL-6 R	3	82	82	N/A	0.08	−0.23 to 0.39	0.60	0.15	0.93	0.0	^70–72
TGF-β
TNF-α
sTNF-R1
2c. Blood cytokine network alterations in chronically ill patients with euthymic bipolar disorder versus controls

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

	Studies	Pt		Control				χ²	P-value

IFN-γ	3	91		122	0.02	−0.26 to 0.30	0.89	3.20	0.36	6.2	^95,101,108
IL-1β	2	125		158	0.31	0.07–0.55	0.01	0.01	0.92	0.0	^105,108
IL-1RA
IL-2	2	46		44	0.18	−0.24 to 0.60	0.40	2.87	0.24	30.3	^95,100
IL-4	3				0.55	0.15–0.95	0.01	58.31	<0.01	94.9	^{95,96,100,95,96,101,103,104}
IL-6	7	213		540	0.30	0.13–0.47	<0.01	27.57	<0.01	78.2	^106,108
IL-8
IL-10	7	166		273	0.26	0.06–0.46	0.01	27.74	<0.01	74.8	^{95,96,100,102–104,108}
IL-12
IL-17
IL-18
sIL-2 R	3	199		230	0.80	0.59–1.00	<0.01	24.63	<0.01	91.9	^93,96,107
sIL-6 R	2	98		153	0.78	0.52–1.05	<0.01	2.14	0.14	53.4	^93,98
TGF-β
TNF-α	7	236		296	0.04	−0.14 to 0.22	0.66	19.08	0.01	58.1	^94,95,99,100
sTNF-R1	4	133		310	0.44	0.19–0.69	<0.01	6.80	0.08	55.9	^{102–104,108}
2d. Blood cytokine network alterations in chronically ill patients with bipolar depression versus controls

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

	Studies	Pt		Control				χ²	P-value

IFN-γ
IL-1β
IL-1RA
IL-2
IL-4
IL-6	3	102		344	0.00	−0.23 to 0.23	0.98	6.94	0.03	71.2	^95,101,103
IL-8
IL-10	2	44		105	0.23	−0.14 to 0.60	0.22	0.80	0.37	0.0	^95,103
IL-12
IL-17
IL-18
sIL-2 R
sIL-6 R
TGF-β
TNF-α	2	44		105	−0.16	−0.53 to 0.21	0.40	1.93	0.16	48.3	^95,103
sTNF-R1	2	72		369	0.25	0.00–0.51	0.05	3.99	0.05	74.9	^91,101

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.