Inhibitory effect of interleukin 4 on production of interleukin 6 by adult T-cell leukemia cells.
Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) produce high levels of interleukin 6 (IL-6), which is suggested to play an important role in thrombocytosis, elevation of C-reactive protein, and hypercalcemia in ATL. In this study, we investigated the effects of T-cell growth factors such as interleukin 2 (IL-2) and interleukin 4 (IL-4) on IL-6 production by ATL cells in vitro. Although IL-2 and/or IL-4 enhanced the cell proliferation of freshly isolated ATL cells from seven of nine patients, IL-2 did not affect the IL-6 release in most cases. In contrast, another T-cell tropic factor, IL-4 markedly inhibited the release of IL-6 in the conditioned medium in all cases. This IL-4-mediated inhibition of IL-6 release was completely abrogated by the addition of anti-IL-4 monoclonal antibody. Time course experiments demonstrated that IL-4 reduced the secretion of IL-6 for a prolonged period of time (more than 72 h). By Northern analysis, IL-4 reduced the transcription level of IL-6 mRNA. Furthermore, by flow cytofluorometry with the use of anti-human IL-4 receptor monoclonal antibody, ATL cells showed the significant level of IL-4 receptor on their cell surfaces without any stimulation. These data suggest that IL-4 may play an important regulatory role in the production of IL-6 in ATL.
Mori
N
N
First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Shirakawa
F
F
Murakami
S
S
Oda
S
S
Eto
S
S
D000368:Aged; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D015458:Leukemia, T-Cell / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000093242:Interleukin-6 Inhibitors
D007376:Interleukin-2; D015847:Interleukin-4; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000093242:Interleukin-6 Inhibitors