Cytokine production in patients with cirrhosis and TLR4 polymorphisms

doi:10.3748/wjg.v20.i46.17516

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Dec 14, 2014; 20(46): 17516-17524
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17516

Table 1 Clinical and analytical characteristics of patients with TLR4 polymorphisms and wild-type patients n (%)

	Polymorphisms (n = 9)	Wild-type (n = 10)	P value
Age (yr)	63.2 (40-78)	61.0 (42-79)	0.93
Sex (male/female)	6 (67)/3 (33)	6 (60)/4 (40)	1.00
Etiology (alcohol/HCV/alcohol + HCV/other)	3 (33)/3 (33)/2 (22)/1 (11)	5 (50)/2 (20)/3 (30)/0 (0)	0.5
Child-Pugh score	7 (5-9)	6 (5-8)	0.49
MELD score	11 (6-16)	12 (6-18)	0.62
Serum bilirubin (μmol/L)	17.0 (7-41)	27.5 (9-60)	0.56
Serum albumin (g/L)	32.8 (22.7-49.4)	35.9 (30.0-43.9)	0.34
INR	1.10 (1.01-1.48)	1.22 (0.96-1.39)	0.68
Blood total leukocyte count (× 10⁹/L)	5.89 (2.75-11.48)	5.67 (3.84-8.57)	0.93
Blood neutrophil count (× 10⁹/L)	3.30 (2.00-7.78)	3.21 (1.61-5.63)	0.74
Blood monocyte count (× 10⁹/L)	0.59 (0.20-0.98)	0.66 (0.38-1.00)	0.46
Blood lymphocyte count (× 10⁹/L)	1.00 (0.38-2.15)	1.41 (0.35-2.22)	0.39
Present ascites	3 (33)	3 (30)	1.00
Diuretics	6 (67)	9 (90)	0.30
Beta-blockers	4 (44)	5 (50)	1.00
Norfloxacin prophylaxis	5 (55)	4 (40)	0.65

HCV: Hepatitis C virus; MELD: Model for end-stage liver disease; INR: International normalized ratio.

Table 2 Data of previous complications of cirrhosis in patients with TLR4 polymorphisms and wild-type patients n (%)

	Polymorphisms (n = 9)	Wild-type (n = 10)	P value
Previous ascites	9 (100)	10 (100)	1.00
Previous variceal bleeding	4 (44)	2 (20)	0.35
Previous bacterial infections	8 (89)	5 (50)	0.14
Number of infections/patient	2.0 (0-4)	0.5 (0-5)	0.14
Previous SBP	5 (55)	3 (30)	0.37
Previous hepatic encephalopathy	7 (78)	2 (20)	0.02
Number of episodes of encephalopathy	17	8
Number of episodes of encephalopathy/patient	1 (0-5)	0 (0-7)	0.03
Degree of encephalopathy (episodes) 1/2/3/4	5/9/1/2	3/4/0/1
Degree of encephalopathy¹	2.0 (1-4)	1.9 (1-4)	0.74

¹Median (range) of the degree of hepatic encephalopathy in patients with this complication. SBP: Spontaneous bacterial peritonitis.

Table 3 Spontaneous and stimulated cytokine production by peripheral blood cells in healthy donors and all patients with cirrhosis

	Healthy donors (n = 5)	All patients with cirrhosis (n = 19)	P value
Spontaneous TNF-α (pg/mL)	< 30	602.4 (96.1-3920.1)	0.001
TNF-α after LPS (pg/mL)	1693 (1185-3709)	2904 (931-5078)	0.150
TNF-α after LTA (pg/mL)	638.3 (49.7-1958)	2440 (241-4798)	0.006
Spontaneous IL-6 (pg/mL)	< 10	1537.8 (172.0-26053.9)	0.001
IL-6 after LPS (pg/mL)	20493 (19499-23042)	30219 (1362-32680)	0.006
IL-6 after LTA (pg/mL)	22157 (17390-27010)	30165 (3269-32707)	0.005
Spontaneous IL-10 (pg/mL)	< 30	43.6 (6.5-318.1)	0.210
IL-10 after LPS (pg/mL)	1309 (590.2-1578)	939.9 (120.8-2100)	0.890
IL-10 after LTA (pg/mL)	499.3 (268.7-816.9)	800.4 (80.72-2077)	0.150

TNF-α: Tumour necrosis factor-alpha; LPS: Lipopolysaccharide; LTA: Lipoteichoic acid; IL: Interleukin.

Table 4 Increment in cytokine production expressed as stimulated/spontaneous production fold change in patients with cirrhosis and TLR4 polymorphisms and wild-type patients

	Polymorphisms (n = 9)	Wild-type (n = 10)	P value
Increment TNF-α after LPS	5.3 (1.0-17.4)	3.8 (1.1-17.0)	0.280
Increment TNF-α after LTA	6.5 (1.2-14.4)	2.7 (0.2-5.1)	0.040
Increment IL-6 after LPS	26.0 (14.7-189.9)	3.3 (1.1-17.0)	< 0.001
Increment IL-6 after LTA	35.2 (15.4-183.6)	3.0 (1.2-25.6)	< 0.001
Increment IL-10 after LPS	37.8 (9.3-185.1)	6.3 (0.5-143.9)	0.006
Increment IL-10 after LTA	32.0 (11.3-70.4)	3.7 (1.0-23.7)	0.002

TNF-α: Tumour necrosis factor-alpha; LPS: Lipopolysaccharide; LTA: Lipoteichoic acid; IL: Interleukin.

Table 5 Spontaneous and stimulated cytokine production by peripheral blood cells in patients with cirrhosis not treated with norfloxacin

	Polymorphisms (n = 4)	Wild-type (n = 6)	P value
Spontaneous TNF-α (pg/mL)	464.3 (223.6-3920.1)	813.1 (591-1573)	0.25
TNF-α after LPS (pg/mL)	3166 (931.8-5078)	2936 (1272-4547)	0.76
TNF-α after LTA (pg/mL)	2766 (2291-4798)	1927 (241.3-4455)	0.17
Spontaneous IL-6 (pg/mL)	699.4 (320.8-1145.6)	5540 (1538-26053.9)	< 0.001
IL-6 after LPS (pg/mL)	27880 (19100-30070)	29000 (24960-32670)	0.47
IL-6 after LTA (pg/mL)	29660 (27970-30290)	29860 (3269-32170)	1.00
Spontaneous IL-10 (pg/mL)	13.2 (6.5-39.1)	135.6 (36.2-318.1)	0.02
IL-10 after LPS (pg/mL)	949.5 (655-1474)	1467 (334.5-2100)	0.35
IL-10 after LTA (pg/mL)	606.8 (376-1234)	897.6 (86.66-1530)	0.91

TNF-α: Tumour necrosis factor-alpha; LPS: Lipopolysaccharide; LTA: Lipoteichoic acid; IL: Interleukin.

Citation: Nieto JC, Sánchez E, Román E, Vidal S, Oliva L, Guarner-Argente C, Poca M, Torras X, Juárez C, Guarner C, Soriano G. Cytokine production in patients with cirrhosis and TLR4 polymorphisms. World J Gastroenterol 2014; 20(46): 17516-17524
URL: https://www.wjgnet.com/1007-9327/full/v20/i46/17516.htm
DOI: https://dx.doi.org/10.3748/wjg.v20.i46.17516