Modulation of Cytokine Production by Drugs with Antiepileptic or Mood Stabilizer Properties in Anti-CD3- and Anti-CD40-Stimulated Blood In Vitro

Table 1

Median, first (1. Qu), and third (3. Qu) quartile of cytokine levels in unstimulated blood, OKT3/5C3-stimulated blood, and OKT3/5C3-stimulated blood with mood stabilizers and AEDs at 1-fold (PRM: 12 𝜇g/mL, CBZ: 10 µg/mL, LEV: 90 𝜇g/mL, LTG: 12 𝜇g/mL, VPA: 100 𝜇g/mL, OXC: 30 𝜇g/mL, TPM: 25 𝜇g/mL, PB: 40 𝜇g/mL, and lithium: 1.2 mmol/L) and 2-fold concentration.

	IL-1𝛽 (pg/mL)
	Median	1. Qu	3. Qu	𝑁
Unstimulated blood	0.01	0.00	0.07	14
OKT3/5C3-stimulated blood†	23.47†	1.74	87.09	13
Concentration	1-fold				2-fold				Sig.
	Median	1. Qu	3. Qu	𝑁	Median	1. Qu	3. Qu	𝑁
PRM	8.55*	2.17	34.22	14	8.09*	0.54	23.13	14	0.279
CBZ	12.08*	0.00	31.05	14	9.21*	0.35	18.37	14	0.279
LEV	12.22*	1.96	30.85	14	7.61*	0.57	25.97	14	0.683
LTG	3.91*	0.22	14.25	14	0.94*	0.00	6.42	14	0.003
VPA	2.36*	0.45	9.20	14	1.70*	0.08	10.07	14	0.480
OXC	6.77*	0.04	29.97	14	2.56*	0.21	21.91	14	0.025
TPM	10.99*	1.68	43.71	14	18.98	3.56	66.84	14	0.177
PB	10.06*	0.12	35.27	14	6.53*	0.08	32.58	14	0.374
Lithium	24.63	2.34	56.06	14	24.40	5.38	92.58	14	0.140
	IL-2 (pg/mL)
	Median	1. Qu	3. Qu	𝑁
Unstimulated blood	0.24	0.00	1.97	14
OKT3/5C3-stimulated blood	18.26†	2.59	88.08	13
Concentration	1-fold				2-fold				Sig.
	Median	1. Qu	3. Qu	𝑁	Median	1. Qu	3. Qu	𝑁
PRM	12.82*	2.70	28.99	14	11.66*	2.90	34.05	14	0.463
CBZ	7.61*	1.42	38.15	14	8.28*	2.17	17.24	14	0.507
LEV	9.74*	3.46	31.38	14	5.22*	1.42	23.64	14	0.055
LTG	3.58*	0.80	15.90	14	2.89*	0.00	12.82	14	0.050
VPA	4.64*	0.50	20.42	14	3.77*	0.77	41.65	14	0.055
OXC	5.79*	1.04	17.20	14	3.87*	0.05	15.75	14	0.021
TPM	6.06*	2.67	25.69	14	10.61*	4.29	19.32	14	0.917
PB	9.13*	0.80	28.85	14	7.28	2.86	33.85	14	0.279
Lithium	22.95	9.79	61.02	14	104.30*	65.10	233.18	14	0.002
	IL-4 (pg/mL)
	Median	1. Qu	3. Qu	𝑁
Unstimulated blood	0.02	0.00	0.17	14
OKT3/5C3-stimulated blood	3.15†	0.26	10.78	13
Concentration	1-fold				2-fold				Sig.
	Median	1. Qu	3. Qu	𝑁	Median	1. Qu	3. Qu	𝑁
PRM	2.83	0.36	9.93	14	2.47	0.40	8.50	14	0.046
CBZ	1.83	0.21	9.43	14	1.13*	0.08	8.43	14	0.158
LEV	2.56	0.62	9.64	14	1.79	0.14	6.89	14	0.010
LTG	0.50*	0.00	8.15	14	0.44*	0.05	2.39	14	0.110
VPA	0.00*	0.00	1.76	14	0.00*	0.00	2.60	14	0.866
OXC	0.79	0.05	10.23	14	0.40	0.05	9.56	14	0.209
TPM	2.10	0.23	12.70	14	2.03	0.56	10.33	14	0.485
PB	2.25	0.47	12.15	14	1.28	0.25	10.66	14	0.007
Lithium	4.33	0.89	14.27	14	5.34*	2.46	11.57	14	0.096
	IL-6 (pg/mL)
	Median	1. Qu	3. Qu	𝑁
Unstimulated blood	0.26	0.02	0.53	14
OKT3/5C3-stimulated blood	380.80†	13.16	865.67	13
Concentration	1-fold				2-fold				Sig.
	Median	1. Qu	3. Qu	𝑁	Median	1. Qu	3. Qu	𝑁
PRM	38.10*	11.03	299.12	14	59.29	3.23	185.31	14	0.300
CBZ	50.13*	4.57	238.95	14	72.53*	16.07	312.94	14	0.972
LEV	73.82*	32.84	206.15	14	56.35*	22.34	267.09	14	0.925
LTG	23.08*	1.63	122.41	14	5.03*	0.82	31.41	14	0.004
VPA	9.36*	1.23	22.32	14	1.46*	0.73	11.38	14	0.177
OXC	27.61*	1.33	165.59	14	7.73*	0.79	65.89	14	0.026
TPM	87.06*	17.34	194.20	14	88.07*	30.94	190.05	14	0.551
PB	75.39*	1.08	226.22	14	53.65	8.98	365.82	14	0.925
Lithium	244.70	20.98	811.36	14	592.21	149.34	1958.24	14	0.016
	IL-17 (pg/mL)
	Median	1. Qu	3. Qu	𝑁
Unstimulated blood	0.00	0.00	0.33	14
OKT3/5C3-stimulated blood	6.99†	1.19	44.19	13
Concentration	1-fold				2-fold				Sig.
	Median	1. Qu	3. Qu	𝑁	Median	1. Qu	3. Qu	𝑁
PRM	8.28	1.14	27.17	14	5.76	1.11	21.36	14	0.039
CBZ	6.95	0.08	26.99	14	4.73*	0.00	27.68	14	0.158
LEV	7.42	0.69	29.47	14	2.98	0.61	29.35	14	0.530
LTG	4.49*	0.00	12.67	14	1.53*	0.06	3.78	14	0.041
VPA	1.08*	0.00	3.36	14	0.70*	0.00	4.61	14	0.286
OXC	5.10	0.56	14.30	14	3.84*	0.00	10.68	14	0.060
TPM	7.30	1.51	31.82	14	9.84	0.52	26.30	14	0.638
PB	8.90	0.30	22.57	14	5.10*	0.27	23.74	14	0.209
Lithium	15.23*	4.26	69.95	14	17.80*	6.60	71.26	14	0.331
	IL-22 (pg/mL)
	Median	1. Qu	3. Qu	𝑁
Unstimulated blood	92.00	92.00	92.00	2
OKT3/5C3-stimulated blood	445.00	278.00	1002.00	7
Concentration	1-fold				2-fold				Sig.
	Median	1. Qu	3. Qu	𝑁	Median	1. Qu	3. Qu	𝑁
PRM	314.00	179.50	733.50	8	273.00	212.00	888.00	7	0.753
CBZ	315.00	231.00	323.00	7	284.50	171.75	1027.75	6	0.753
LEV	246.00	131.50	382.00	8	365.50	263.50	1353.50	6	0.043
LTG	317.00	182.50	1839.75	4	348.00	106.50	1046.00	5	0.068
VPA	374.00	180.00		3	68.00	47.50	749.00	5	0.109
OXC	321.00	128.25	1094.75	6	222.00	126.00	1152.50	5	0.144
TPM	376.00	179.25	1183.25	6	305.00	85.25	1260.75	8	0.893
PB	336.00	266.50	1935.00	5	414.00	315.25	1099.25	6	0.465
Lithium	576.00	335.00	909.50	9	803.00*	312.00	1317.00	11	0.028
	TNF-𝛼 (pg/mL)
	Median	1. Qu	3. Qu	𝑁
Unstimulated blood	0.00	0.00	0.28	14
OKT3/5C3-stimulated blood	92.80†	1.80	503.56	13
Concentration	1-fold				2-fold				Sig.
	Median	1. Qu	3. Qu	𝑁	Median	1. Qu	3. Qu	𝑁
PRM	206.87	11.68	540.99	14	167.15	17.03	530.13	14	0.470
CBZ	149.75	12.89	388.72	14	93.72	7.44	307.18	14	0.701
LEV	121.55	21.20	379.89	14	81.81	9.87	452.42	14	0.917
LTG	48.31	2.01	203.86	14	14.90	0.00	76.64	14	0.272
VPA	7.28*	0.72	31.57	14	8.37*	0.60	64.47	14	0.583
OXC	88.64	0.32	352.93	14	83.95	1.21	442.08	14	0.861
TPM	133.71	22.48	542.04	14	240.79	15.32	887.72	14	0.008
PB	99.87	4.69	589.68	14	100.96	4.92	385.65	14	0.754
Lithium	326.25	43.69	912.04	14	364.50*	85.15	1027.79	14	0.019

𝑁 = number of measurable cytokines. †Significant difference between cytokine values in unstimulated and OKT3/5C3-stimulated blood. *Significant difference between cytokine values in OKT3/5C3-stimulated blood and OKT3/5C3-stimulated blood with supplementation of the listed drugs at specified concentrations. Sig.: level of significance of the difference between cytokine values at the 1-fold and cytokine values at the 2-fold drug concentration.