PROSPECTIVE MEASUREMENT OF CIRCULATING CYTOKINES IN AUTOIMMUNE HEPATITIS DURING IMMUNOSUPPRESSIVE TREATMENT

22 Cytokines are mediators released by mononuclear cells and likely to play a major pathogenic role in autoimmune hepatitis (AIH), a disease whose histological hallmark is a heavy mononuclear cell infiltrate. Using in-house established ELISAs, we measured IFN-γ (T helper 1 [Th1] related), IL-4 and IL-10 (Th2 related) and TNF-α (macrophage produced) in 23 children with AIH (12 males, median age 10 years [range 2-15], 16 ANA/SMA; 7 LKM positive) at diagnosis and during immuno-suppressive treatment [(median duration of treatment 16 months, median number of observations 6 (range 3-14)] with Prednisolone (Pred) alone or with Azathioprine (AZT). 29 healthy children (15 males, median age 2 yrs, 2 days-13 yrs) were studied as controls. The levels of TNF-α, IFN-γ, IL-4 and IL-10 were higher in patients with AIH than in controls (p<0.001 for all). At diagnosis the levels of aminotransferase (AST), IFN-γ and TNF-α were: 349 IU/I (24-1956), 50 pg/ml (0-3568) and 976 pg/ml (0-6166) respectively, declining during treatment and being significantly lower at the last observation than at diagnosis (29 IU/I [11-80] p<0.001; 0 pg/ml [0-2722]), p<0.004 and 225 pg/ml [0-6564], p<0.008 respectively). Levels of IL-4 and IL-10 remained high during treatment and were similar at diagnosis (412 pg/ml [0-2060]; 1192 pg/ml [0-2697]) and at the last observation (406 pg/ml [0-1986]; 1020 pg/ml [0-3133], p=not significant). The patients who required both Pred and AZT had pretreatment cytokine levels higher than those who required Pred alone (p<0.05 for all). Cytokine levels were similar in ANA/SMA and in LKM positive AIH patients. The drug induced reduction of the proinflammatory TNF-α and IFN-γ may account for the clinical improvement of the patients.