The influence of hepatocellular function on NK and T cell tumoricidal activity

P. T.M. Roughneen, S. Kulkarni, S. C. Kumar, A. D. Kulkarni, W. Fanslow, N. R. Pellis, B. J. Rowlands

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Abstract

Recent studies by this group have demonstrated that hepatocellular integrity is important in the preservation of host cellular immune function. This study evaluated the effect of experimental hepatocellular dysfunction (EHD) on host antineoplastic defense mechanisms. In nonspecific immune studies, we examined the effect of EHD on Wistar Furth (WF) natural killer (NK) cell cytotoxicity; in specific immune studies, we assessed WF C3H/HeJ lymphocytic responsiveness to both T cell mitogen and unmodified syngeneic fibrosarcoma. In concurrent studies, we evaluated the effect of EHD on interleukin-2 (IL-2) synthesis, an important NK and T cell trophic factor. WF rats and C3H/HeJ mice were assigned to three groups: EHD induced by bile duct ligation, sham, and normal control (NC). At day 21 serum bilirubin, WF NK cytotoxicity to YAC-1 tumor cells, WF and C3H/HeJ lymphocytic responsiveness to phytohemagglutinin (PHA) and syngeneic MCA-fibrosarcoma (MCA-F), and WF T-helper IL-2 production were determined in respective groups. Serum total bilirubin was elevated in EHD rats and mice with respect to controls (p < 0.01). Wistar Furth cytotoxicity to the YAC-1 tumor cells was depressed in EHD animals with respect to sham and NC groups at 12.5:1 (p < 0.05), 50:1 (p < 0.05), and 100:1 (p < 0.05) effector/target cell ratios. WF T cell responsiveness to PHA was depressed in EHD with respect to controls (p < 0.01). C3H/HeJ lymphoproliferative response to MCA-F tumor antigen was also depressed in EHD animals when compared with control groups with the addition of 12.5 x 103 (p < 0.05) and 50 x 103 (p < 0.05) MCA-F cells. These impairments in NK and T cell function in EHD could not be attributed to diminished IL-2 production (EHD vs sham and NC: 112,141 ± 5232 vs 106,691 ± 1419 and 120,759 ± 3248 cpm, respectively). These results demonstrate that hepatocellular failure compromises NK and T cell tumoricidal function, an effect not resultant on diminished T helper IL-2 production.

Original languageEnglish (US)
Pages (from-to)888-893
Number of pages6
JournalSurgery
Volume104
Issue number5
StatePublished - Jan 1 1988
Externally publishedYes

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ASJC Scopus subject areas

  • Surgery

Cite this

Roughneen, P. T. M., Kulkarni, S., Kumar, S. C., Kulkarni, A. D., Fanslow, W., Pellis, N. R., & Rowlands, B. J. (1988). The influence of hepatocellular function on NK and T cell tumoricidal activity. Surgery, 104(5), 888-893.