Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 May;88(2):207–212. doi: 10.1111/j.1365-2249.1992.tb03063.x

IL-6 in malignant pleural effusions and its augmentation by intrapleural instillation of IL-2.

H Yanagawa 1, S Sone 1, M Munekata 1, S Atagi 1, A Nii 1, T Ogura 1
PMCID: PMC1554304  PMID: 1315227

Abstract

The levels and activities of endogenous IL-6 in malignant pleural effusions due to lung cancer before and during daily intrapleural instillations of recombinant IL-2 were examined by enzyme immunoassay and bioassay using an IL-6-dependent murine hybridoma cell line MH60.BSF2. Before therapy, malignant pleural effusions contained various levels of IL-6. Daily intrapleural instillation of recombinant IL-2 for treatment of malignant pleurisy resulted in significant augmentation of the levels and activities of IL-6 in the pleural effusions. On fractionation of the pleural effusion by chromatography, one major peak of material with a mol. wt of 24 kD showed IL-6 activity. In contrast, no significant level of tumour necrosis factor-alpha or IL-1 beta was detectable in pleural effusions before or during local IL-2 therapy. These data suggest that IL-2 is an important regulatory factor of secondary IL-6 production.

Full text

PDF
207

Selected References

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

  1. Bauer J., Ganter U., Geiger T., Jacobshagen U., Hirano T., Matsuda T., Kishimoto T., Andus T., Acs G., Gerok W. Regulation of interleukin-6 expression in cultured human blood monocytes and monocyte-derived macrophages. Blood. 1988 Oct;72(4):1134–1140. [PubMed] [Google Scholar]
  2. Boccoli G., Masciulli R., Ruggeri E. M., Carlini P., Giannella G., Montesoro E., Mastroberardino G., Isacchi G., Testa U., Calabresi F. Adoptive immunotherapy of human cancer: the cytokine cascade and monocyte activation following high-dose interleukin 2 bolus treatment. Cancer Res. 1990 Sep 15;50(18):5795–5800. [PubMed] [Google Scholar]
  3. Erroi A., Sironi M., Chiaffarino F., Chen Z. G., Mengozzi M., Mantovani A. IL-1 and IL-6 release by tumor-associated macrophages from human ovarian carcinoma. Int J Cancer. 1989 Nov 15;44(5):795–801. doi: 10.1002/ijc.2910440508. [DOI] [PubMed] [Google Scholar]
  4. Grimm E. A., Mazumder A., Zhang H. Z., Rosenberg S. A. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982 Jun 1;155(6):1823–1841. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Helfgott D. C., May L. T., Sthoeger Z., Tamm I., Sehgal P. B. Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of beta 2 interferon by human fibroblasts. J Exp Med. 1987 Nov 1;166(5):1300–1309. doi: 10.1084/jem.166.5.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Helfgott D. C., Tatter S. B., Santhanam U., Clarick R. H., Bhardwaj N., May L. T., Sehgal P. B. Multiple forms of IFN-beta 2/IL-6 in serum and body fluids during acute bacterial infection. J Immunol. 1989 Feb 1;142(3):948–953. [PubMed] [Google Scholar]
  7. Hirano T., Matsuda T., Turner M., Miyasaka N., Buchan G., Tang B., Sato K., Shimizu M., Maini R., Feldmann M. Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol. 1988 Nov;18(11):1797–1801. doi: 10.1002/eji.1830181122. [DOI] [PubMed] [Google Scholar]
  8. Hirano T., Taga T., Yasukawa K., Nakajima K., Nakano N., Takatsuki F., Shimizu M., Murashima A., Tsunasawa S., Sakiyama F. Human B-cell differentiation factor defined by an anti-peptide antibody and its possible role in autoantibody production. Proc Natl Acad Sci U S A. 1987 Jan;84(1):228–231. doi: 10.1073/pnas.84.1.228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Horii Y., Muraguchi A., Iwano M., Matsuda T., Hirayama T., Yamada H., Fujii Y., Dohi K., Ishikawa H., Ohmoto Y. Involvement of IL-6 in mesangial proliferative glomerulonephritis. J Immunol. 1989 Dec 15;143(12):3949–3955. [PubMed] [Google Scholar]
  10. 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]
  11. Jablons D. M., Mulé J. J., McIntosh J. K., Sehgal P. B., May L. T., Huang C. M., Rosenberg S. A., Lotze M. T. IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans. J Immunol. 1989 Mar 1;142(5):1542–1547. [PubMed] [Google Scholar]
  12. Kato K., Yamada T., Kawahara K., Onda H., Asano T., Sugino H., Kakinuma A. Purification and characterization of recombinant human interleukin-2 produced in Escherichia coli. Biochem Biophys Res Commun. 1985 Jul 31;130(2):692–699. doi: 10.1016/0006-291x(85)90472-3. [DOI] [PubMed] [Google Scholar]
  13. Kawano M., Hirano T., Matsuda T., Taga T., Horii Y., Iwato K., Asaoku H., Tang B., Tanabe O., Tanaka H. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature. 1988 Mar 3;332(6159):83–85. doi: 10.1038/332083a0. [DOI] [PubMed] [Google Scholar]
  14. Kishimoto T. The biology of interleukin-6. Blood. 1989 Jul;74(1):1–10. [PubMed] [Google Scholar]
  15. Matsuda T., Hirano T., Kishimoto T. Establishment of an interleukin 6 (IL 6)/B cell stimulatory factor 2-dependent cell line and preparation of anti-IL 6 monoclonal antibodies. Eur J Immunol. 1988 Jun;18(6):951–956. doi: 10.1002/eji.1830180618. [DOI] [PubMed] [Google Scholar]
  16. May L. T., Ghrayeb J., Santhanam U., Tatter S. B., Sthoeger Z., Helfgott D. C., Chiorazzi N., Grieninger G., Sehgal P. B. Synthesis and secretion of multiple forms of beta 2-interferon/B-cell differentiation factor 2/hepatocyte-stimulating factor by human fibroblasts and monocytes. J Biol Chem. 1988 Jun 5;263(16):7760–7766. [PubMed] [Google Scholar]
  17. Miki S., Iwano M., Miki Y., Yamamoto M., Tang B., Yokokawa K., Sonoda T., Hirano T., Kishimoto T. Interleukin-6 (IL-6) functions as an in vitro autocrine growth factor in renal cell carcinomas. FEBS Lett. 1989 Jul 3;250(2):607–610. doi: 10.1016/0014-5793(89)80805-1. [DOI] [PubMed] [Google Scholar]
  18. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  19. Mulé J. J., McIntosh J. K., Jablons D. M., Rosenberg S. A. Antitumor activity of recombinant interleukin 6 in mice. J Exp Med. 1990 Mar 1;171(3):629–636. doi: 10.1084/jem.171.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Muraguchi A., Kishimoto T., Miki Y., Kuritani T., Kaieda T., Yoshizaki K., Yamamura Y. T cell-replacing factor- (TRF) induced IgG secretion in a human B blastoid cell line and demonstration of acceptors for TRF. J Immunol. 1981 Aug;127(2):412–416. [PubMed] [Google Scholar]
  21. Nakamura Y., Ozaki T., Yanagawa H., Yasuoka S., Ogura T. Eosinophil colony-stimulating factor induced by administration of interleukin-2 into the pleural cavity of patients with malignant pleurisy. Am J Respir Cell Mol Biol. 1990 Oct;3(4):291–300. doi: 10.1165/ajrcmb/3.4.291. [DOI] [PubMed] [Google Scholar]
  22. Nijsten M. W., de Groot E. R., ten Duis H. J., Klasen H. J., Hack C. E., Aarden L. A. Serum levels of interleukin-6 and acute phase responses. Lancet. 1987 Oct 17;2(8564):921–921. doi: 10.1016/s0140-6736(87)91413-9. [DOI] [PubMed] [Google Scholar]
  23. Nishida T., Nishino N., Takano M., Kawai K., Bando K., Masui Y., Nakai S., Hirai Y. cDNA cloning of IL-1 alpha and IL-1 beta from mRNA of U937 cell line. Biochem Biophys Res Commun. 1987 Feb 27;143(1):345–352. doi: 10.1016/0006-291x(87)90671-1. [DOI] [PubMed] [Google Scholar]
  24. Rawle F. C., Shields J., Smith S. H., Iliescu V., Merkenschlager M., Beverley P. C., Callard R. E. B cell growth and differentiation induced by supernatants of transformed epithelial cell lines. Eur J Immunol. 1986 Aug;16(8):1017–1019. doi: 10.1002/eji.1830160825. [DOI] [PubMed] [Google Scholar]
  25. Rosenberg S. A. Immunotherapy of cancer using interleukin 2: current status and future prospects. Immunol Today. 1988 Feb;9(2):58–62. doi: 10.1016/0167-5699(88)91261-3. [DOI] [PubMed] [Google Scholar]
  26. Sone S., Nakanishi M., Ohmoto Y., Yanagawa H., Ogura T. Macrophage colony-stimulating factor activity in malignant pleural effusions. Its augmentation by intrapleural interleukin-2 infusions. Chest. 1991 Feb;99(2):377–381. doi: 10.1378/chest.99.2.377. [DOI] [PubMed] [Google Scholar]
  27. Takai Y., Wong G. G., Clark S. C., Burakoff S. J., Herrmann S. H. B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes. J Immunol. 1988 Jan 15;140(2):508–512. [PubMed] [Google Scholar]
  28. Tanaka K., Ishikawa E., Ohmoto Y., Hirai Y. In vitro production of human interleukin 1 alpha and interleukin 1 beta by peripheral blood mononuclear cells examined by sensitive sandwich enzyme immunoassay. Eur J Immunol. 1987 Oct;17(10):1527–1530. doi: 10.1002/eji.1830171024. [DOI] [PubMed] [Google Scholar]
  29. Van Meir E., Sawamura Y., Diserens A. C., Hamou M. F., de Tribolet N. Human glioblastoma cells release interleukin 6 in vivo and in vitro. Cancer Res. 1990 Oct 15;50(20):6683–6688. [PubMed] [Google Scholar]
  30. Watson J. M., Sensintaffar J. L., Berek J. S., Martínez-Maza O. Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures. Cancer Res. 1990 Nov 1;50(21):6959–6965. [PubMed] [Google Scholar]
  31. Yanagawa H., Sone S., Nii A., Fukuta K., Nakanishi M., Maeda K., Honda M., Ogura T. Lymphokine-activated killer induction and its regulation by macrophages in malignant pleural effusions. Jpn J Cancer Res. 1989 Dec;80(12):1220–1227. doi: 10.1111/j.1349-7006.1989.tb01658.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yoshizaki K., Matsuda T., Nishimoto N., Kuritani T., Taeho L., Aozasa K., Nakahata T., Kawai H., Tagoh H., Komori T. Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman's disease. Blood. 1989 Sep;74(4):1360–1367. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES