Infective mortality is common in children who have hepatic failure. We have demonstrated that experimental hepatic failure (EHF) profoundly suppresses T cell function in vivo. To determine the basis for immune suppression in EHF we postulated that this phenomenon is attributable to alterations in accessory macrophage (Ma) function, T cell subsets, interleukin-2 (IL-2) production, or serum inhibition. Wistar Furth rats (200 g) were randomized to EHF (n = 23), Sham (n = 23), and normal control (NC) (n = 23) groups. On day 21, splenocytes and sera were harvested and immune assays performed in vitro. Following are the results (mean ± SEM; Student's t test). Serum bilirubin was elevated in EHF versus Sham and NC groups (P <.01). EHF splenic macrophages suppressed PHA when added to microcultures at 105 concentration (-140 ± 550 v 12,263 ± 2,492 [Sham] and 21,413 ± 1,702 [NC] P <.01). This effect was not evident when macrophages were added back to microcultures at 103 and 104 concentrations, suggesting a dose-dependent inhibitory effect. T helper: suppressor ratios did not differ in EHF (1.3 ± 0.2) compared with Sham (1.4 ± 0.2) and NC groups (1.2 ± 0.1). IL-2 production was similar in EHF, Sham, and NC animals (112,141 ± 5,232 versus 106,691 ± 1,419 and 120,759 ± 3,249 counts per minute). T cell inhibitory activity was not demonstrable in EHF sera. These data show that splenic macrophages can inhibit T cell function in vitro. This phenomenon may be paramount in predisposing children with liver disease to infection.
- Hepatic failure
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