The antiviral drug amantadine has a direct inhibitory effect on T-lymphocytes.
We investigated the effect of the antiviral drug amantadine (AmTd) on polyclonal activation of thymic-dependent (T) and thymic-independent (B) lymphocytes from normal mice. In the present studies, T-lymphocytes are defined by their response to concanavalin A (Con A) and B-lymphocytes by their response to lipopolysaccharide (LPS). Polyclonal activator-induced lymphocyte proliferation was assessed by quantifying cellular incorporation of tritiated thymidine. The results show that, in a dose-dependent manner, AmTd exhibits at least 2-fold greater inhibitory activity against Con A-responding T-cells than against LPS-responding B-cells. Further, several findings demonstrate that AmTd has a direct inhibitory effect on T-lymphocytes. First, AmTd pulse treatment of isolated T-cells, but not accessory cells, abolished the T-cell response to Con A. Second, AmTd pulse treatment of the cytotoxic T-lymphocyte line, CTLL-2, markedly reduced their ability to undergo IL-2-induced proliferation. Third, proliferation of T-cells which had already undergone activation by ConA was inhibited by AmTd. Further, the finding that addition of IL-1, IL-2 or both to cultures failed to reverse inhibition of the response to ConA argues that AmTd did not interfere with endogenous production of these lymphokines. Possible implications of these findings are discussed.
Clark
C
C
Medical Research Division, Veterans Administration Medical Center, Minneapolis, MN 55417.
Woodson
M M
MM
Winge
V B
VB
Nagasawa
H T
HT
D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects*
D007376:Interleukin-2; D008070:Lipopolysaccharides; D008222:Lymphokines; D003208:Concanavalin A; D000547:Amantadine