Levamisole regulates the proliferation of murine liver T cells through Kupffer-cell-derived cytokines |
| |
Authors: | John A Johnkoski Steven M Peterson R J Doerr S A Cohen |
| |
Institution: | (1) Department of Surgery, Veterans Administration Medical Center, 3495 Bailey Avenue, Buffalo, NY 14215, USA, US;(2) Department of Medicine, Veterans Administration Medical Center, 3495 Bailey Avenue, Buffalo, NY 14215, USA Fax: 716 862 3419;, US;(3) Department of Surgery, Buffalo General Hospital, 100 High Street, Buffalo, NY 14203, USA, US;(4) Department of Surgery, Veterans Administration Medical Center, 3495 Bailey Avenue, Buffalo, NY 14215, USA, US |
| |
Abstract: | We have previously shown that levamisole increases the cytotoxic, cytostatic, and proliferative activity of murine nonparenchymal
liver cells (NPC) in vitro. We have also shown that the nonadherent subpopulation of NPC, which are composed predominantly
of T lymphocytes, is very responsive to this agent when administered to mice. Kupffer cells or immigrant macrophages are also
responsive to levamisole but to a lesser extent. These findings prompted us to investigate changes in cytokine production
by NPC following-treatment of mice with levamisole (25 mg/kg, i.p.), which may help explain the observed alterations in the
immune functions of these cells. We found that levamisole treatment of mice causes a threefold increase in production of interferon
(IFN) α/β by adherent NPC (more than 80% – 90% Kupffer cells) in vitro. When IFN α/β was added to cultured cells, it decreased
the proliferative capacity of liver T cells in a dose-dependent manner. In contrast, the addition of anti-IFNα/β was shown
to augment levamisole-induced proliferation of unfractionated NPC and Kupffer cells. NPC production of interleukin 1 (IL-1)
and interleukin-6 (IL-6) in vitro was also increased threefold following treatment of mice with levamisole. IL-6 added in
vitro to cells significantly augmented levamisole-induced proliferation of liver T cells while anti-IL-6 reduced proliferative
activity to control levels. These findings suggested that IFNα/β, IL-6, and IL-1 play important regulatory roles in controlling
the proliferative response of murine liver-associated T lymphocytes to levamisole. Finally, the proliferation of bone marrow
cells was increased in mice given 5-fluorouracil (5FU). On the other hand, the proliferation of NPC was dramatically suppressed
when 5FU was administered. However, the proliferation of these cells was restored when levamisole was given after 5FU.
Received: 27 November 1995 / Accepted: 16 October 1996 |
| |
Keywords: | Levamisole 5-Fluorouracil Cytokines Kupffer cells Liver T cells |
本文献已被 SpringerLink 等数据库收录! |
|