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. 1997 Apr;6(2):147–153. doi: 10.1080/09629359791857

Interleukin-6 and interleukin-6 receptor secretion by chronic lymphatic leukaemia and normal B lymphocytes: effect of PMA and PWM

I Drucker 1, A Klajman 1,✉, M Revel 2, Y Manor 3, S Ben-Efraim 4, D Novick 2
PMCID: PMC2365853  PMID: 18472849

Abstract

Interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) were detected in supernatants of cultures of B chronic lymphatic leukaemia (CLL) lymphocytes. Phorbol-12-myristate 13 acetate (PMA) caused a decrease in the levels of IL-6 in 14 out of 16 cultures and an increase in levels of sIL6R in all 15 cases. The effect of pokeweed mitogen (PWM) was variable and not significant. The levels of IL-6 were below the detection limit (60 pg/ml) in sera of 13 CLL patients whereas sIL-6R was detected (13 ng/ml to 97 ng/ml) in the 13 sera. IL6 was not detected in cultures of unstimulated or stimulated with PMA or PWM normal human B cells. Levels of sIL-6R were minimal in cultures of normal B lymphocytes and were increased in PMA stimulated cultures. The results are consistent with the view that B-CLL cells produce spontaneously IL-6 which could act in an autocrine fashion to cause shedding of surface IL-6R and account for the correlation found between serum levels of sIL-6R and B-CLL lymphocyte numbers. The fall in levels of IL-6 in PMA stimulated CLL cultures might express masking or degradation of IL-6 after combination with the receptor.

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Selected References

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  1. Biondi A., Rossi V., Bassan R., Barbui T., Bettoni S., Sironi M., Mantovani A., Rambaldi A. Constitutive expression of the interleukin-6 gene in chronic lymphocytic leukemia. Blood. 1989 Apr;73(5):1279–1284. [PubMed] [Google Scholar]
  2. Engelmann H., Novick D., Wallach D. Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors. J Biol Chem. 1990 Jan 25;265(3):1531–1536. [PubMed] [Google Scholar]
  3. Farkas R., Ben-Efraim S., Manor Y., Zan-Bar I., Klajman A. Appearance of the T-cell marker CD8 on B chronic lymphatic leukemia cells in long-term cultures. Cancer Immunol Immunother. 1991;34(3):181–185. doi: 10.1007/BF01742310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Farkas R., Manor Y., Klajman A. Long-term cultures of chronic lymphocytic leukemia B cells generate B suppressor cells. Clin Immunol Immunopathol. 1987 Feb;42(2):171–182. doi: 10.1016/0090-1229(87)90004-3. [DOI] [PubMed] [Google Scholar]
  5. Garman R. D., Jacobs K. A., Clark S. C., Raulet D. H. B-cell-stimulatory factor 2 (beta 2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7629–7633. doi: 10.1073/pnas.84.21.7629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986 Nov 6;324(6092):73–76. doi: 10.1038/324073a0. [DOI] [PubMed] [Google Scholar]
  7. Horii Y., Muraguchi A., Suematsu S., Matsuda T., Yoshizaki K., Hirano T., Kishimoto T. Regulation of BSF-2/IL-6 production by human mononuclear cells. Macrophage-dependent synthesis of BSF-2/IL-6 by T cells. J Immunol. 1988 Sep 1;141(5):1529–1535. [PubMed] [Google Scholar]
  8. Kishimoto T., Akira S., Taga T. IL-6 receptor and mechanism of signal transduction. Int J Immunopharmacol. 1992 Apr;14(3):431–438. doi: 10.1016/0192-0561(92)90173-i. [DOI] [PubMed] [Google Scholar]
  9. Kishimoto T. The biology of interleukin-6. Blood. 1989 Jul;74(1):1–10. [PubMed] [Google Scholar]
  10. Levy Y., Fermand J. P., Brouet J. C. Differential effects of low and high concentrations of interleukin 6 on human B cells. Eur J Immunol. 1990 Nov;20(11):2389–2393. doi: 10.1002/eji.1830201105. [DOI] [PubMed] [Google Scholar]
  11. Maliszewski C. R., Fanslow W. C. Soluble receptors for IL-1 and IL-4: biological activity and therapeutic potential. Trends Biotechnol. 1990 Nov;8(11):324–329. doi: 10.1016/0167-7799(90)90213-h. [DOI] [PubMed] [Google Scholar]
  12. Matsuzaki N., Saji F., Kameda T., Yoshizaki K., Okada T., Sawai K., Tanizawa O. In vitro and in vivo production of interleukin-6 by fetal mononuclear cells. Clin Immunol Immunopathol. 1990 May;55(2):305–314. doi: 10.1016/0090-1229(90)90106-z. [DOI] [PubMed] [Google Scholar]
  13. Müllberg J., Schooltink H., Stoyan T., Günther M., Graeve L., Buse G., Mackiewicz A., Heinrich P. C., Rose-John S. The soluble interleukin-6 receptor is generated by shedding. Eur J Immunol. 1993 Feb;23(2):473–480. doi: 10.1002/eji.1830230226. [DOI] [PubMed] [Google Scholar]
  14. Navarro S., Debili N., Le Couedic J. P., Klein B., Breton-Gorius J., Doly J., Vainchenker W. Interleukin-6 and its receptor are expressed by human megakaryocytes: in vitro effects on proliferation and endoreplication. Blood. 1991 Feb 1;77(3):461–471. [PubMed] [Google Scholar]
  15. Nordan R. P., Potter M. A macrophage-derived factor required by plasmacytomas for survival and proliferation in vitro. Science. 1986 Aug 1;233(4763):566–569. doi: 10.1126/science.3726549. [DOI] [PubMed] [Google Scholar]
  16. Novick D., Cohen B., Rubinstein M. Soluble interferon-alpha receptor molecules are present in body fluids. FEBS Lett. 1992 Dec 21;314(3):445–448. doi: 10.1016/0014-5793(92)81523-o. [DOI] [PubMed] [Google Scholar]
  17. Novick D., Engelmann H., Revel M., Leitner O., Rubinstein M. Monoclonal antibodies to the soluble human IL-6 receptor: affinity purification, ELISA, and inhibition of ligand binding. Hybridoma. 1991 Feb;10(1):137–146. doi: 10.1089/hyb.1991.10.137. [DOI] [PubMed] [Google Scholar]
  18. Novick D., Engelmann H., Wallach D., Rubinstein M. Soluble cytokine receptors are present in normal human urine. J Exp Med. 1989 Oct 1;170(4):1409–1414. doi: 10.1084/jem.170.4.1409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Novick D., Eshhar Z., Revel M., Mory Y. Monoclonal antibodies for affinity purification of IL-6/IFN- beta 2 and for neutralization of HGF activity. Hybridoma. 1989 Oct;8(5):561–567. doi: 10.1089/hyb.1989.8.561. [DOI] [PubMed] [Google Scholar]
  20. Novick D., Shulman L. M., Chen L., Revel M. Enhancement of interleukin 6 cytostatic effect on human breast carcinoma cells by soluble IL-6 receptor from urine and reversion by monoclonal antibody. Cytokine. 1992 Jan;4(1):6–11. doi: 10.1016/1043-4666(92)90029-q. [DOI] [PubMed] [Google Scholar]
  21. Rai K. R., Sawitsky A., Cronkite E. P., Chanana A. D., Levy R. N., Pasternack B. S. Clinical staging of chronic lymphocytic leukemia. Blood. 1975 Aug;46(2):219–234. [PubMed] [Google Scholar]
  22. Rieckmann P., D'Alessandro F., Nordan R. P., Fauci A. S., Kehrl J. H. IL-6 and tumor necrosis factor-alpha. Autocrine and paracrine cytokines involved in B cell function. J Immunol. 1991 May 15;146(10):3462–3468. [PubMed] [Google Scholar]
  23. Yoshizaki K., Nakagawa T., Fukunaga K., Tseng L. T., Yamamura Y., Kishimoto T. Isolation and characterization of B cell differentiation factor (BCDF) secreted from a human B lymphoblastoid cell line. J Immunol. 1984 Jun;132(6):2948–2954. [PubMed] [Google Scholar]

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