title: A potential basis for suppressed inflammatory cell function in pediatric cholestatic hosts.
abstract: 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 less than .01). EHF splenic macrophages suppressed PHA when added to microcultures at 10(5) concentration (-140 +/- 550 v 12,263 +/- 2,492 [Sham] and 21,413 +/- 1,702 [NC] P less than .01). This effect was not evident when macrophages were added back to microcultures at 10(3) and 10(4) 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.
authors: Department of Surgery, University of Texas Medical School, Houston 77030.
authors: P T
authors: PT
authors: Roughneen
authors: A D
authors: AD
authors: Kulkarni
authors: R J
authors: RJ
authors: Andrassy
authors: B J
authors: BJ
authors: Rowlands
mesh_terms: D000818:Animals; D002779:Cholestasis / Q000097:blood / Q000473:pathology*; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis*; D007958:Leukocyte Count; D008107:Liver Diseases / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D011920:Rats, Inbred WF; D013154:Spleen / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D007376:Interleukin-2; D010835:Phytohemagglutinins