Recombinant IL-4 inhibits IL-6 synthesis by adherent peripheral blood cells in vitro.
IL-4 has been shown to participate in interregulatory networks with other cytokines including IL-2, IFN-gamma, IL-1 beta, and TNF-alpha. The ability of recombinant IL-4 (rIL-4) to modulate the synthesis and release of IL-6 was investigated in vitro. LPS-stimulated adherent cells (AC) from human peripheral blood secreted IL-6 as determined by ELISA and bioassay with the B9 hybridoma cell line. The secretion of IL-6 peaked between 12-16 h after LPS stimulation. The addition of rIL-4 inhibited LPS-induced IL-6 production measured at 8 h. The inhibitory effect of rIL-4 on IL-6 secretion was dose-dependent and occurred at doses as low as 0.001 U/ml (0.01 pg/ml). Recombinant IL-4 was added to the cultures for various periods and removed by aspiration of the medium and washing the cells. The subsequent LPS-induction of IL-6 secretion was reduced in cultures exposed to rIL-4 for as little as 5 minutes indicating that the effect of rIL-4 on the monocytes was rapid and irreversible. Northern blot analysis revealed that the effect of rIL4 on LPS-induced production of IL-6 by AC occurred at least in part at the level of transcription. In contrast, PMA-induced IL-6 gene transcription was not affected by rIL-4. These findings indicate that rIL-4 can regulate the synthesis of IL-6 by adherent peripheral blood mononuclear cells.
Gibbons
R
R
Department of Surgery, University of California Medical Center, San Francisco.
Martinez
O
O
Matli
M
M
Heinzel
F
F
Bernstein
M
M
Warren
R
R
D000210:Acute-Phase Reaction / Q000276:immunology; D002448:Cell Adhesion; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate
D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate