Cytokine profiles in patients receiving antioxidant therapy within the ANTICIPATE trial

Table 1 Demographic profiles

Variables	Antioxidant (n = 7)	Placebo (n = 7)	P value
Age (yr), median (range)	46 (34-79)	46 (37-60)	0.92 (Mann-Whitney U)
Gender (male:female)	5:2	4:3	0.90 (Fisher’s exact)
Aetiology	Alcohol 6; idiopathic 1	Alcohol 4; idiopathic 3	0.55 (Fisher’s exact)
Disease duration (yr)	4 (1-5)	3 (2-13)	0.92 (Mann-Whitney U)
Body mass index (kg/m2)	24.2 (18.8-36.7)	22.5 (22.9-32.8)	0.62 (Mann-Whitney U)
Alcohol (g/d), median (range)	175.5 (0-396)	138.6 (0-252)	0.43 (Mann-Whitney U)
Cigarette smoker (Y:N)	6:1	5:2	0.59 (Fisher’s exact)
Diabetes mellitus (Y:N)	2:5	1:6	0.62 (Fisher’s exact)
Faecal elastase (μg/g)	68 (15-500)	27 (15-500)	0.27 (Mann-Whitney U)
Opiate use (mg/d)	40 (30-300)	85 (0-120)	0.30 (Mann-Whitney U)

Laboratory reference range for faecal elastase report values < 200 μg/g as representing end-stage exocrine failure. All opiate intakes are reported as morphine equivalent.

Table 2 Baseline antioxidant profiles

Variables	Antioxidant (n = 7)	Placebo (n = 7)	Laboratory reference range	Median difference	P value (MWU)	95%CI
Vitamin C (μg/mL)	7.7 (0.7-13)	5.8 (2.4-9.9)	4-20	1.6	0.53	-3-6.1
Vitamin E (mg/L)	12.4 (5.4-20.9)	5.4 (3.6-15.2)	5.7-14.9	4.4	0.12	-2.6-11.1
β-carotene (mol/L)	35.9 (8-87)	11.6 (7-233)	19-254	15	0.55	-166-71
Vitamin A (mg/L)	0.60 (0.30-0.68)	0.40 (0.20-0.57)	0.4-1.2	0.16	0.07	-0.03-0.37
Selenium (μg/L)	82 (27-110)	49 (27-97)	83-152	27	0.22	-14-53
WGSH (μmol/L)	1361 (1229-1682)	1336 (1149-1585)	1078-1753	62.5	0.73	-118-290
WGSH/Hb (μmol/g)	9.2 (7.8-11.4)	9.7 (8.9-10.0)	7.5-12.2	-0.3	0.70	-1.4-1.5
WCC (109/L)	7.7 (6.4-10.3)	10 (5-15.9)	4-11	-1.4	0.38	-4.4-2.2
Hb (g/dL)	14.9 (13.4-15.8)	13.7 (12.4-16)	13-18	1	0.33	-0.6-2.1
CRP (mg/L)	3 (3-29)	7 (3-29)	0.3-5	-1	0.27	-7-3

WGSH: Whole blood glutathione; WGSH/Hb: Glutathione corrected for haemoglobin concentration; WCC: White cell count; Hb: Haemoglobin; CRP: C-reactive protein; MWU: Mann-Whitney U.

Table 3 Antioxidant profiles at 6 mo compared to baseline

Variables	Antioxidant (n = 7)	Placebo (n = 7)	P value (antioxidant vs baseline)	95%CI	P value (antioxidant vs placebo )	95%CI
Vitamin C (μg/mL)	17.6 (12.8-29.3)	4.8 (1.6-9.1)	0.001	-18.8-6.5	< 0.001	9.0-20.2
Vitamin E (mg/L)	17.8 (11.7-25.0)	5.0 (4.0-4.6)	0.160	-1.8-12.3	0.004	4.4-14.3
β-carotene (mol/L)	155.5 (23-478)	38.1 (8-204)	0.150	-189-35	0.244	-20-190
Vitamin A (mg/L)	0.5 (0.42-0.72)	0.3 (0.25-0.64)	0.910	-0.19-0.14	0.010	0.05-0.34
Selenium (μg/L)	109 (95-133)	48 (40-92)	0.007	-75-14	< 0.001	41-85
WCC (109/L)	6.7 (4.9-10.8)	7.4 (6-10.8)	0.330	-1.3-3.2	0.600	-3.3-1.9
Hb (g/dL)	14.2 (13.5-16.0)	12.7 (12.3-16.0)	0.510	-1-1.6	0.150	-1.3-2.6
CRP (mg/L)	3 (3-4)	6 (3-10)	0.190	0-3	0.070	-7-0
Opiate usage	20	55	0.210	-40-79	0.630	-56-60

WGSH: Whole blood glutathione; WGSH/Hb: Glutathione corrected for haemoglobin concentration; WCC: White cell count; Hb: Haemoglobin; CRP: C-reactive protein.

Table 4 Cytokine levels in patients receiving antioxidant therapy compared to placebo

Cytokine	Laboratory range	Antioxidant therapy baseline (pg/mL)	Placebo baseline (pg/mL)	P value	95%CI	Antioxidant therapy at 6 mo (pg/mL)	Placebo at 6 mo (pg/mL)	P value	95%CI
IL-1β1	1.6-250	< 1.6	< 1.6			< 1.6	< 1.6
IL-2	4.8-3000	2.6 (0-4.8)	3.1 (0-3.5)	0.83	-1.1-1.7	2.6 (0.0-4.8)	2.9 (0.0-3.2)	0.97	-2.6-2.3
IL-4	6.6-900	2.3 (2.2-6.6)	2.5 (2.1-6.6)	0.84	-3.7-3.9	2.5 (2.2-6.6)	2.8 (2.1-6.6)	0.81	-1.3-3.7
IL-6	1.2-900	1.9 (0.8-3.5)	1.8 (0.7-8.9)	0.99	-2.6-1.4	1.6 (1.0-2.3)	1.4 (0.9-7.6)	0.78	-3.9-0.7
IL-8	4.9-3000	10.1 (8.1-23.7)	8.5 (7.5-19.8)	0.46	-5.2-8.4	11.6 (8.1-19.3)	10.8 (6.6-18.6)	0.54	-2.7-18.7
IL-102	1.8-1000	< 0.6	< 0.6			< 0.6	< 0.6
TNFα	4.4-1500	3.5 (2.4-5.8)	3.5 (2.2-4.9)	0.71	-1.1-1.6	3.8 (2.4-4.7)	3.4 (2.5-4.5)	0.40	-0.7-1.1
IL-18	0-3000	388.6 (245.7-818.9)	457.9 (317.5-775.7)	0.71	-228-165	365.5 (211.5-879.8)	435.7 (349.1-570.1)	0.40	-238-299
VEGF	14.6-3000	116.2 (49.8-191.2)	243.1 (39.5-305.5)	0.32	-187-51	93.7 (35.1-173.9)	184.4 (34.1-299.9)	0.22	-206-34.7
EGF	2.9-900	28.4 (9.8-137.7)	23.4 (11.9-75.6)	0.99	-30.0-47.6	9.4 (3.1-65.2)	34.4 (2.3-139.8)	0.09	-66.8-5.5
MCP-1	13.2-1500	335.9 (267.1-423)	298.8 (229.5-685.1)	0.81	-134-106	296.5 (235.0-426.7)	326.4 (265.5-468.6)	0.38	-127-49

¹All patients had interleukin (IL)-1β levels below the lower threshold of detection. IL-2: Antioxidant group at 6 mo vs antioxidant group at baseline, P = 0.64 (95%CI: -1.5-2.5); IL-4: Antioxidant group at 6 mo vs antioxidant group at baseline, P = 0.89 (95%CI: -3.7-3.7); IL-6: Antioxidant group at 6 mo vs antioxidant group at baseline, P = 0.25 (95%CI: -0.4-1.7); IL-8: Antioxidant group at 6 mo vs antioxidant group at baseline, P = 0.69 (95%CI: -17.8-4.9);

²All patients had interleukin 10 below the lower threshold of detection. Transforming growth factor type β1 (TGFβ1): Antioxidant group at 6 mo vs antioxidant group at baseline, P = 0.46 (95%CI: -39-74); tumor necrosis factor α (TNFα): Antioxidant group at 6 mo vs antioxidant group at baseline, P = 0.97 (95%CI: -1.0-1.4); vascular endothelial growth factor (VEGF): Antioxidant group at 6 mo vs antioxidant group at baseline, P = 0.54 (95%CI: -43.8- 81.0); epidermal growth factor (EGF): Antioxidant group at 6 mo vs antioxidant group at baseline, P = 0.05 (95%CI: -0.22-59.8); monocyte chemotactic protein-1 (MCP-1): Antioxidant group at 6 mo vs antioxidant group at baseline, P = 0.05 (95%CI: -50.1-100.9).