Evans, C.D.J.; Robertson, S.E.; Gracie, J.A.; McInnes, I.B.; Morris, A.J.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA1
Academic Journal
Aim and Background: IL-18 is a novel pro-inflammatory cytokine of the IL-1 family and is critical in the development of Th-1 responses. Th-1 responses have been implicated in the pathogenesis of ALD. We investigated IL-18 expression in patients with ALD and AH. Patients and Methods: We studied inpatients with ALD (n = 48, I/P ALD), outpatients with compensated ALD (n = 13, O/P ALD), and healthy volunteers (n = 15, HVs). The mean age of the I/P ALD (40 males) was 47.7 years and that of the O/P ALD group 55.2 years. Other forms of chronic liver disease were excluded by standard serological tests. IL-18 levels were measured by ELISA (Diaclone). Whole blood cell culture (WBC) +/-lipopolysacchoride (LPS) was performed to assess lL-18 production. A Childs-Pugh score and a Maddrey's Discriminant Function were calculated for all patients. The results were analysed by Mann-Whitney U test. Results: Inpatients consisted of five with Childs grade A, 17 B, and 26 C. Eighteen had a MDF < 24, 9 a MDF of 24-32, and 21 a MDF > 32. Plasma IL-18 levels were significantly elevated in the I/P ALD group when compared with O/P ALD and HVs (all units pg/ml), (174 +/- 170, 45 +/- 52, and 32 +/- 83; p < 0.01 and p < 0.001). IL-18 levels in Child's C inpatients (226 +/- 214) were significantly elevated compared to Child's A inpatients (27 +/- 38; p < 0.01). Higher plasma IL-18 levels were found in inpatients with moderate/ severe AH (MDF > 24) when compared with inpatients with MDF < 24, O/P ALDs, and HVs (224 +/- 203, 93 +/- 89, 45 +/- 83, and 32 +/- 52; p < 0.02, p < 0.002, and p < 0.0001, respectively). Patients with Childs grades B/C showed no incremental rise in lL-18 production following LPS stimulation. A similar result was obtained on analysis of patients with moderate/severe AH (206 +/- 190 to 217 +/- 214). Conclusions: Plasma IL-18 is elevated in patients with ALD. IL-18 levels are higher in patients with increasing severity of ALD (Childs grade B/C) and AH (MDF > 24). In...


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