Inhibition of human mononuclear cell proliferation, interleukin synthesis, mRNA for IL-2, IL-6, and leukotriene B4 synthesis by a lipoxygenase inhibitor.
Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro with various stimuli and in the presence or absence of a 5-lipoxygenase (5-LO) inhibitor, A-63162, to measure its effects on PBMC proliferation, interleukin-2 receptor (IL-2R) expression, interleukin-2 (IL-2) synthesis, interleukin-6 (IL-6) synthesis, and accumulation of messenger RNA for IL-2 or IL-6. A-63162 inhibited PBMC proliferation stimulated by phytohemagglutinin (PHA) and phorbol myristate acetate (PMA) plus A23187, IL-2 receptor expression stimulated by PHA, and IL-2 or IL-6 synthesis induced by PHA plus PMA or PMA plus A23187. At the same concentration, A-63162 inhibited accumulation of mRNA for IL-2 or IL-6 and also inhibited leukotriene B4 (LTB4) synthesis. Our data indicate that the 5-LO inhibitor A-63162 has immunosuppressive activity that may be due to inhibition of LTB4 production or to direct inhibitory actions of A-63162 on IL-2 and IL-6 synthesis.
Atluru
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D
Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota 55404.
Gudapaty
S
S
O'Donnell
M P
MP
Woloschak
G E
GE
D000081:Acetamides / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007975:Leukotriene B4 / Q000096:biosynthesis* / Q000097:blood; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D010647:Phenyl Ethers; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000081:Acetamides; D007376:Interleukin-2; D015850:Interleukin-6; D016859:Lipoxygenase Inhibitors; D010647:Phenyl Ethers; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; C068663:N-hydroxy-N-(1-(4-(phenylmethoxy)phenyl)ethyl)-acetamide; D007975:Leukotriene B4; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate