A potential basis for suppressed inflammatory cell function in pediatric cholestatic hosts.
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.
Roughneen
P T
PT
Department of Surgery, University of Texas Medical School, Houston 77030.
Kulkarni
A D
AD
Andrassy
R J
RJ
Rowlands
B J
BJ
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*
D007376:Interleukin-2; D010835:Phytohemagglutinins