Skip to main content
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1995 May;48(5):482–487. doi: 10.1136/jcp.48.5.482

Effect of interleukins on the proliferation and survival of B cell chronic lymphocytic leukaemia cells.

T Mainou-Fowler 1, J A Copplestone 1, A G Prentice 1
PMCID: PMC502630  PMID: 7629299

Abstract

AIMS--To investigate the effects of interleukin (IL) 1, 2, 4, and 5 on the proliferation and survival of peripheral blood B cells from patients with B chronic lymphocytic leukaemia (B-CLL) and compare them with the effects on normal peripheral blood B cells. METHODS--The proliferation and survival of pokeweed mitogen (PWM) activated B cells from B-CLL (n = 12) and normal peripheral blood (n = 5) were studied in vitro in response to IL-1, IL-2 IL-4, and IL-5. Survival of cells in cultures with or without added interleukins was studied by microscopic examination of cells and DNA agarose gel electrophoresis. RESULTS--Proliferation was observed in both B-CLL and normal peripheral blood cells on culture with IL-2 alone and also in some, but not all, B-CLL and normal peripheral blood cells with IL-1 and IL-4. However, there was greater variability in B-CLL cell responses than in normal peripheral blood cells. Il-5 did not affect normal peripheral blood cell proliferation but it increased proliferation in two B-CLL cases. Synergistic effects of these cytokines were not detected. IL-4 inhibited normal peripheral blood and B-CLL cell proliferation after the addition of IL-2. Inhibition of B-CLL cell responses to IL-2 was also observed with IL-5 and Il-1. Survival of B-CLL cells in cultures was enhanced with IL-4 not by an increase in proliferation but by reduced apoptosis. No such effect was seen in normal peripheral blood cells. IL-2 had a less noticeable antiapoptotic effect; IL-5 enhanced apoptosis in B-CLL cells. CONCLUSIONS--B-CLL and normal peripheral blood cells proliferated equally well in response to IL-2. IL-4 had a much lower effect on B-CLL cell proliferation, but had noticeable antiapoptotic activity. IL-5 enhanced cell death by apoptosis.

Full text

PDF
482

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alvarez-Mon M., de la Hera A., Gaspar M. L., Orfao A., Casas J., Jordá J., Durantez A. Proliferation of B cells from chronic lymphocytic leukemia is selectively promoted by B cell growth factor. Acta Haematol. 1989;81(2):91–97. doi: 10.1159/000205533. [DOI] [PubMed] [Google Scholar]
  2. Arai K. I., Lee F., Miyajima A., Miyatake S., Arai N., Yokota T. Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem. 1990;59:783–836. doi: 10.1146/annurev.bi.59.070190.004031. [DOI] [PubMed] [Google Scholar]
  3. Arends M. J., Morris R. G., Wyllie A. H. Apoptosis. The role of the endonuclease. Am J Pathol. 1990 Mar;136(3):593–608. [PMC free article] [PubMed] [Google Scholar]
  4. Benjamin D., Bazar L. S., Wallace B., Jacobson R. J. Heterogeneity of B-cell growth factor receptor reactivity in healthy donors and in patients with chronic lymphatic leukemia: relationship to B-cell-derived lymphokines. Cell Immunol. 1986 Dec;103(2):394–408. doi: 10.1016/0008-8749(86)90099-7. [DOI] [PubMed] [Google Scholar]
  5. Callard R. E. Immunoregulation by interleukin-4 in man. Br J Haematol. 1991 Jul;78(3):293–299. doi: 10.1111/j.1365-2141.1991.tb04439.x. [DOI] [PubMed] [Google Scholar]
  6. Dancescu M., Rubio-Trujillo M., Biron G., Bron D., Delespesse G., Sarfati M. Interleukin 4 protects chronic lymphocytic leukemic B cells from death by apoptosis and upregulates Bcl-2 expression. J Exp Med. 1992 Nov 1;176(5):1319–1326. doi: 10.1084/jem.176.5.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Defrance T., Vanbervliet B., Aubry J. P., Takebe Y., Arai N., Miyajima A., Yokota T., Lee F., Arai K., de Vries J. E. B cell growth-promoting activity of recombinant human interleukin 4. J Immunol. 1987 Aug 15;139(4):1135–1141. [PubMed] [Google Scholar]
  8. Dighiero G., Travade P., Chevret S., Fenaux P., Chastang C., Binet J. L. B-cell chronic lymphocytic leukemia: present status and future directions. French Cooperative Group on CLL. Blood. 1991 Oct 15;78(8):1901–1914. [PubMed] [Google Scholar]
  9. Freedman A. S., Boyd A. W., Bieber F. R., Daley J., Rosen K., Horowitz J. C., Levy D. N., Nadler L. M. Normal cellular counterparts of B cell chronic lymphocytic leukemia. Blood. 1987 Aug;70(2):418–427. [PubMed] [Google Scholar]
  10. Hansson M. Growth and differentiation factors for B and T cells. Leuk Res. 1990;14(8):705–710. doi: 10.1016/0145-2126(90)90098-t. [DOI] [PubMed] [Google Scholar]
  11. Hivroz C., Grillot-Courvalin C., Brouet J. C., Seligmann M. Heterogeneity of responsiveness of chronic lymphocytic leukemic B cells to B cell growth factor or interleukin 2. Eur J Immunol. 1986 Aug;16(8):1001–1004. doi: 10.1002/eji.1830160821. [DOI] [PubMed] [Google Scholar]
  12. Jelinek D. F., Lipsky P. E. Enhancement of human B cell proliferation and differentiation by tumor necrosis factor-alpha and interleukin 1. J Immunol. 1987 Nov 1;139(9):2970–2976. [PubMed] [Google Scholar]
  13. Karray S., Dautry-Varsat A., Tsudo M., Merle-Beral H., Debre P., Galanaud P. IL-4 inhibits the expression of high affinity IL-2 receptors on monoclonal human B cells. J Immunol. 1990 Aug 15;145(4):1152–1158. [PubMed] [Google Scholar]
  14. Karray S., DeFrance T., Merle-Béral H., Banchereau J., Debré P., Galanaud P. Interleukin 4 counteracts the interleukin 2-induced proliferation of monoclonal B cells. J Exp Med. 1988 Jul 1;168(1):85–94. doi: 10.1084/jem.168.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Karray S., Merle-Béral H., Vazquez A., Gerard J. P., Debre P., Galanaud P. Functional heterogeneity of B-CLL lymphocytes: dissociated responsiveness to growth factors and distinct requirements for a first activation signal. Blood. 1987 Oct;70(4):1105–1110. [PubMed] [Google Scholar]
  16. Karray S., Vazquez A., Merle-Beral H., Olive D., Debre P., Galanaud P. Synergistic effect of recombinant IL 2 and interferon-gamma on the proliferation of human monoclonal lymphocytes. J Immunol. 1987 Jun 1;138(11):3824–3828. [PubMed] [Google Scholar]
  17. Koury M. J., Bondurant M. C. Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science. 1990 Apr 20;248(4953):378–381. doi: 10.1126/science.2326648. [DOI] [PubMed] [Google Scholar]
  18. McConkey D. J., Orrenius S., Jondal M. Cellular signalling in programmed cell death (apoptosis). Immunol Today. 1990 Apr;11(4):120–121. doi: 10.1016/0167-5699(90)90048-e. [DOI] [PubMed] [Google Scholar]
  19. Mingari M. C., Gerosa F., Carra G., Accolla R. S., Moretta A., Zubler R. H., Waldmann T. A., Moretta L. Human interleukin-2 promotes proliferation of activated B cells via surface receptors similar to those of activated T cells. Nature. 1984 Dec 13;312(5995):641–643. doi: 10.1038/312641a0. [DOI] [PubMed] [Google Scholar]
  20. Moberts R., Hoogerbrugge H., van Agthoven T., Löwenberg B., Touw I. Proliferative response of highly purified B chronic lymphocytic leukemia cells in serum free culture to interleukin-2 and tumor necrosis factors alpha and beta. Leuk Res. 1989;13(11):973–980. doi: 10.1016/0145-2126(89)90004-0. [DOI] [PubMed] [Google Scholar]
  21. Ojeda F., Guarda M. I., Maldonado C., Folch H. Protein kinase-C involvement in thymocyte apoptosis induced by hydrocortisone. Cell Immunol. 1990 Feb;125(2):535–539. doi: 10.1016/0008-8749(90)90106-2. [DOI] [PubMed] [Google Scholar]
  22. Panayiotidis P., Ganeshaguru K., Jabbar S. A., Hoffbrand A. V. Interleukin-4 inhibits apoptotic cell death and loss of the bcl-2 protein in B-chronic lymphocytic leukaemia cells in vitro. Br J Haematol. 1993 Nov;85(3):439–445. doi: 10.1111/j.1365-2141.1993.tb03330.x. [DOI] [PubMed] [Google Scholar]
  23. Paul W. E. Interleukin-4: a prototypic immunoregulatory lymphokine. Blood. 1991 May 1;77(9):1859–1870. [PubMed] [Google Scholar]
  24. Perri R. T. Impaired expression of cell surface receptors for B cell growth factor by chronic lymphocytic leukemia B cells. Blood. 1986 Apr;67(4):943–948. [PubMed] [Google Scholar]
  25. Pistoia V., Cozzolino F., Rubartelli A., Torcia M., Roncella S., Ferrarini M. In vitro production of interleukin 1 by normal and malignant human B lymphocytes. J Immunol. 1986 Mar 1;136(5):1688–1692. [PubMed] [Google Scholar]
  26. Raff M. C. Social controls on cell survival and cell death. Nature. 1992 Apr 2;356(6368):397–400. doi: 10.1038/356397a0. [DOI] [PubMed] [Google Scholar]
  27. Swain S. L., Dutton R. W. Production of a B cell growth-promoting activity, (DL)BCGF, from a cloned T cell line and its assay on the BCL1 B cell tumor. J Exp Med. 1982 Dec 1;156(6):1821–1834. doi: 10.1084/jem.156.6.1821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Touw I., Dorssers L., Löwenberg B. The proliferative response of B cell chronic lymphocytic leukemia to interleukin 2: functional characterization of the interleukin 2 membrane receptors. Blood. 1987 Jun;69(6):1667–1673. [PubMed] [Google Scholar]
  29. Uggla C., Aguilar-Santelises M., Rosén A., Mellstedt H., Jondal M. Spontaneous production of interleukin 1 activity by chronic lymphocytic leukemic cells. Blood. 1987 Dec;70(6):1851–1857. [PubMed] [Google Scholar]
  30. Vazquez A., Mills S., Maizel A. Modulation of IL-2-induced human B cell proliferation in the presence of human 50-kDa B cell growth factor and IL-4. J Immunol. 1989 Jan 1;142(1):94–99. [PubMed] [Google Scholar]
  31. Williams G. T., Smith C. A., McCarthy N. J., Grimes E. A. Apoptosis: final control point in cell biology. Trends Cell Biol. 1992 Sep;2(9):263–267. doi: 10.1016/0962-8924(92)90198-v. [DOI] [PubMed] [Google Scholar]
  32. Williams G. T., Smith C. A., Spooncer E., Dexter T. M., Taylor D. R. Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature. 1990 Jan 4;343(6253):76–79. doi: 10.1038/343076a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES