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 g/mL, CBZ: 10 µg/mL, LEV: 90 g/mL, LTG: 12 g/mL, VPA: 100 g/mL, OXC: 30 g/mL, TPM: 25 g/mL, PB: 40 g/mL, and lithium: 1.2 mmol/L) and 2-fold concentration.
IL-1 (pg/mL)
Median
1. Qu
3. Qu
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
Median
1. Qu
3. Qu
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
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
Median
1. Qu
3. Qu
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
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
Median
1. Qu
3. Qu
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
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
Median
1. Qu
3. Qu
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
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
Median
1. Qu
3. Qu
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
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
Median
1. Qu
3. Qu
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- (pg/mL)
Median
1. Qu
3. Qu
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
Median
1. Qu
3. Qu
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
= 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.