Interleukin-6 functions as an intracellular growth factor in hairy cell leukemia in vitro.
The role of interleukin-6 (IL-6) in the growth of B cell derived hairy cell leukemia (HCL) was characterized. Purified hairy cells (HCs) did not increase DNA synthesis in vitro in response to exogenous IL-6; however, they expressed IL-6 receptor (IL-6R) mRNA and bound directly fluorochrome labeled IL-6. IL-6 mRNA was not detectable in tumor cells by Northern blotting, but was evident using PCR amplification. Although intracytoplasmic IL-6 protein was not demonstrable, HCs did secrete low levels of IL-6. Neutralizing antibody to IL-6 did not inhibit HC DNA synthesis. Since tumor necrosis factor (TNF) is a growth factor for HCL, we determined whether the TNF effect could be IL-6-mediated. TNF markedly augmented in vitro DNA synthesis by HCs. TNF did not alter IL-6R expression or IL-6 binding; however, IL-6 mRNA and IL-6 protein were detectable after 3-d culture of HCs with TNF. In addition, IL-6 secretion by HCs was markedly augmented by TNF. Finally, although neither IL-6 nor anti-IL-6 antibody altered TNF-induced DNA synthesis by HCs, IL-6 antisense oligonucleotide inhibited TNF-induced DNA synthesis and IL-6 secretion by HCs. Therefore, IL-6 does not directly affect the growth of HCL, but rather mediates TNF-induced DNA synthesis via an intracytoplasmic mechanism.
Barut
B
B
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Chauhan
D
D
Uchiyama
H
H
Anderson
K C
KC
D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000378:metabolism*; D002469:Cell Separation; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D007943:Leukemia, Hairy Cell / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000378:metabolism; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000954:Antigens, Surface; D006133:Growth Substances; D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha