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Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1990 Jan;31(1):49–52. doi: 10.1007/BF01742495

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

G Gallagher 1,, W H Stimson 1, J Findlay 2, F Al-Azzawi 2
PMCID: PMC11038205  PMID: 2407352

Abstract

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.

Keywords: Cancer Research, Mononuclear Cell, Peripheral Blood Mononuclear Cell, Killer Cell, Cell Development

References

  • 1.Al-Azzawi F, Stimson WH, Govan ADT. Human antibodies to ovarian cancer antigens secreted by lymphoblastoid cell lines. J Clin Lab Immunol. 1987;22:71. [PubMed] [Google Scholar]
  • 2.Andus T, Geiger T, Hirano T, Northoff H, Ganter U, Baner J, Kishimoto T, Heinrich PG. Recombinant human B-cell stimulatory factor 2 (BSF2/IFN-β2) regulates β-fibrinogen and albumin mRNA levels in Fao-9 cells. FEBS Lett. 1987;221:18. doi: 10.1016/0014-5793(87)80344-7. [DOI] [PubMed] [Google Scholar]
  • 3.Brookes B, Rees RC. Recombinant IL-4 suppresses the induction of human IL-2 induced lymphokine-activated killer (LAK) activity. Clin Exp Immunol. 1988;74:162. [PMC free article] [PubMed] [Google Scholar]
  • 4.Gallagher G, Taylor N, Willdridge J. Separate but complementary roles for the two forms of interleukin-1 in the growth of transformed human B lymphoblasts. Scand J Immunol. 1987;26:295. doi: 10.1111/j.1365-3083.1987.tb02263.x. [DOI] [PubMed] [Google Scholar]
  • 5.Gallagher G, Wilcox F, Al-Azzawi F. Interleukin-3 and interleukin-4 each strongly inhibit the induction of human LAK-cells. Clin Exp Immunol. 1988;74:166. [PMC free article] [PubMed] [Google Scholar]
  • 6.Geiger T, Andus T, Klapproth J, Hirano T, Kishimoto T, Heinrich PC. Induction of rat acute phase proteins by interleukin 6 in vivo. Eur J Immunol. 1988;18:717. doi: 10.1002/eji.1830180510. [DOI] [PubMed] [Google Scholar]
  • 7.Ikebuchi K, Wong GG, Clark SC, Ilke JN, Hirai Y, Ogawa M. Interleukin-6 enhancement of interleukin-3-dependent proliferation of multipotential haemopoietic progenitors. Proc Natl Acad Sci USA. 1987;84:9035. doi: 10.1073/pnas.84.24.9035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Mosmann T. A rapid colorimetric assay for cellular proliferation and survival. J Immunol Methods. 1983;65:55. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  • 9.Mule JJ, Schwarz SL, Roberts AB, Sporn MB, Rosenberg SA. Transforming growth factor β inhibits the in vitro generation of lymphokine-activated killer cells and cytotoxic T cells. Cancer Immunol Immunother. 1988;26:95. doi: 10.1007/BF00205600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Nijstein MWN, DeGroot ER, Ten Duis HJ, Klasen HJ, Hack CE, Aarden L. Serum levels of IL-6 and acute phase responses. Lancet. 1987;ii:21. doi: 10.1016/s0140-6736(87)91413-9. [DOI] [PubMed] [Google Scholar]
  • 11.Ochoa AC, Gromo G, Alter BJ, Sandel PM, Bach FH. Long-term growth of lymphokine-activated killer (LAK) cells: role of anti-CD3, β-IL-1, interferon γ and IFN-β. J Immunol. 1987;138:2728. [PubMed] [Google Scholar]
  • 12.Okada M, Kitahara M, Kishimoto S, Matsuda T, Hirano T, Kishimoto T. IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T-cells. J Immunol. 1988;141:1543. [PubMed] [Google Scholar]
  • 13.Papa MB, Mule JJ, Rosenberg SA. 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. 1986;46:4973. [PubMed] [Google Scholar]
  • 14.Rosenberg SA, Lotze MT. Cancer immunotherapy using interleukin-2 and interleukin-2 activated lymphocytes. Annu Rev Immunol. 1986;4:681. doi: 10.1146/annurev.iy.04.040186.003341. [DOI] [PubMed] [Google Scholar]
  • 15.Rosenberg SA, Lotze MT, Mule LM, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985;313:1485. doi: 10.1056/NEJM198512053132327. [DOI] [PubMed] [Google Scholar]
  • 16.van Oers MJH, van der Heyden, Aarden LA. A novel interleukin in serum and urine of renal transplant recipients. Dev Biol Stand. 1987;69:39. [PMC free article] [PubMed] [Google Scholar]
  • 17.Wong GG, Clark SC. Multiple actions of interleukin-6 within a cytokine network. Immunol Today. 1988;9:137. doi: 10.1016/0167-5699(88)91200-5. [DOI] [PubMed] [Google Scholar]

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