Cancer Immunology, Immunotherapy

, Volume 31, Issue 1, pp 49–52 | Cite as

Interleukin-6 enhances the induction of human lymphokine-activated killer cells

  • G. Gallagher
  • W. H. Stimson
  • J. Findlay
  • F. Al-Azzawi
Original articles


Human peripheral blood mononuclear cells develop a powerful lytic capacity when cultured in vitro with interleukin-2 (IL-2), becoming lymphokine-activated killer cells (LAK cells). As part of an investigation into means of influencing this process, the effect of other cytokines has been examined. In this study we describe the ability of interleukin-6 (IL-6) to regulate the induction and function of human LAK cells. The results show that substitution of IL-6 for IL-2 did not lead to the development of functional LAK cells, nor was IL-6 able to alter the lytic capacity of established LAK cells. However, when IL-6 was included with IL-2 during the induction phase of the LAK cells, the resulting cells displayed considerably greater lytic activity than those prepared with IL-2 alone. This effect was IL-6 dose-related. These results indicate that LAK cell development may be positively regulated in vitro; the implications of this observation for the clinical usage of LAK cells are discussed.


Cancer Research Mononuclear Cell Peripheral Blood Mononuclear Cell Killer Cell Cell Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Al-Azzawi F, Stimson WH, Govan ADT (1987) Human antibodies to ovarian cancer antigens secreted by lymphoblastoid cell lines. J Clin Lab Immunol 22: 71Google Scholar
  2. 2.
    Andus T, Geiger T, Hirano T, Northoff H, Ganter U, Baner J, Kishimoto T, Heinrich PG (1987) Recombinant human B-cell stimulatory factor 2 (BSF2/IFN-β2) regulates β-fibrinogen and albumin mRNA levels in Fao-9 cells. FEBS Lett 221: 18Google Scholar
  3. 3.
    Brookes B, Rees RC (1988) Recombinant IL-4 suppresses the induction of human IL-2 induced lymphokine-activated killer (LAK) activity. Clin Exp Immunol 74: 162Google Scholar
  4. 4.
    Gallagher G, Taylor N, Willdridge J (1987) Separate but complementary roles for the two forms of interleukin-1 in the growth of transformed human B lymphoblasts. Scand J Immunol 26: 295Google Scholar
  5. 5.
    Gallagher G, Wilcox F, Al-Azzawi F (1988) Interleukin-3 and interleukin-4 each strongly inhibit the induction of human LAK-cells. Clin Exp Immunol 74: 166Google Scholar
  6. 6.
    Geiger T, Andus T, Klapproth J, Hirano T, Kishimoto T, Heinrich PC (1988) Induction of rat acute phase proteins by interleukin 6 in vivo. Eur J Immunol 18: 717Google Scholar
  7. 7.
    Ikebuchi K, Wong GG, Clark SC, Ilke JN, Hirai Y, Ogawa M (1987) Interleukin-6 enhancement of interleukin-3-dependent proliferation of multipotential haemopoietic progenitors. Proc Natl Acad Sci USA 84: 9035Google Scholar
  8. 8.
    Mosmann T (1983) A rapid colorimetric assay for cellular proliferation and survival. J Immunol Methods 65: 55Google Scholar
  9. 9.
    Mule JJ, Schwarz SL, Roberts AB, Sporn MB, Rosenberg SA (1988) Transforming growth factor β inhibits the in vitro generation of lymphokine-activated killer cells and cytotoxic T cells. Cancer Immunol Immunother 26: 95Google Scholar
  10. 10.
    Nijstein MWN, DeGroot ER, Ten Duis HJ, Klasen HJ, Hack CE, Aarden L (1987) Serum levels of IL-6 and acute phase responses. Lancet ii: 21Google Scholar
  11. 11.
    Ochoa AC, Gromo G, Alter BJ, Sandel PM, Bach FH (1987) Long-term growth of lymphokine-activated killer (LAK) cells: role of anti-CD3, β-IL-1, interferon γ and IFN-β. J Immunol 138: 2728Google Scholar
  12. 12.
    Okada M, Kitahara M, Kishimoto S, Matsuda T, Hirano T, Kishimoto T (1988) IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T-cells. J Immunol 141: 1543Google Scholar
  13. 13.
    Papa MB, Mule JJ, Rosenberg SA (1986) Anti-tumour efficacy of lymphokine-activated killer cells and recombinant interleukin-2 in vivo: successful immunotherapy of established pulmonary metastases from weakly immunogenic and nonimmunogenic murine tumours of three distinct histological types. Cancer Res 46: 4973Google Scholar
  14. 14.
    Rosenberg SA, Lotze MT (1986) Cancer immunotherapy using interleukin-2 and interleukin-2 activated lymphocytes. Annu Rev Immunol 4: 681Google Scholar
  15. 15.
    Rosenberg SA, Lotze MT, Mule LM et al. (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and interleukin-2 to patients with metastatic cancer. N Engl J Med 313: 1485Google Scholar
  16. 16.
    van Oers MJH, van der Heyden, Aarden LA (1987) A novel interleukin in serum and urine of renal transplant recipients. Dev Biol Stand 69: 39Google Scholar
  17. 17.
    Wong GG, Clark SC (1988) Multiple actions of interleukin-6 within a cytokine network. Immunol Today 9: 137Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • G. Gallagher
    • 1
  • W. H. Stimson
    • 1
  • J. Findlay
    • 2
  • F. Al-Azzawi
    • 2
  1. 1.Immunology DivisionUniversity of Strathclyde, The Todd CentreGlasgowUK
  2. 2.Addenbrookes HospitalUniversity of CambridgeCambridgeUK

Personalised recommendations