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British Journal of Cancer logoLink to British Journal of Cancer
. 1992 Jul;66(1):204–210. doi: 10.1038/bjc.1992.243

Recombinant human interleukin 4 (IL-4) given as daily subcutaneous injections--a phase I dose toxicity trial.

M H Gilleece 1, J H Scarffe 1, A Ghosh 1, C M Heyworth 1, E Bonnem 1, N Testa 1, P Stern 1, T M Dexter 1
PMCID: PMC1977892  PMID: 1637669

Abstract

Recombinant Interleukin 4 was administered by subcutaneous injection at daily doses of 0.5, 1.0 or 5.0 micrograms kg-1 to nine patients as part of a Phase I Dose Toxicity Study. Dose limiting toxicity was reached at 5 micrograms kg-1 day-1. Symptoms of toxicity included fatigue, 'flu like symptoms and elevated liver enzymes. Modest but significant elevations of neutrophil and platelet counts occurred. No clear evidence of antitumour effects emerged although pain in metastatic lymph nodes and a small fall in myeloma paraprotein levels during dosing were observed. In vitro and murine in vivo studies indicate that patients with lymphoproliferative disease should be selected for Phase II trials.

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Selected References

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  1. Bosco M., Giovarelli M., Forni M., Modesti A., Scarpa S., Masuelli L., Forni G. Low doses of IL-4 injected perilymphatically in tumor-bearing mice inhibit the growth of poorly and apparently nonimmunogenic tumors and induce a tumor-specific immune memory. J Immunol. 1990 Nov 1;145(9):3136–3143. [PubMed] [Google Scholar]
  2. Broxmeyer H. E., Lu L., Cooper S., Tushinski R., Mochizuki D., Rubin B. Y., Gillis S., Williams D. E. Synergistic effects of purified recombinant human and murine B cell growth factor-1/IL-4 on colony formation in vitro by hematopoietic progenitor cells. Multiple actions. J Immunol. 1988 Dec 1;141(11):3852–3862. [PubMed] [Google Scholar]
  3. Cabrillat H., Galizzi J. P., Djossou O., Arai N., Yokota T., Arai K., Banchereau J. High affinity binding of human interleukin 4 to cell lines. Biochem Biophys Res Commun. 1987 Dec 31;149(3):995–1001. doi: 10.1016/0006-291x(87)90507-9. [DOI] [PubMed] [Google Scholar]
  4. Cairns J. A., Gordon J. Intact, 45-kDa (membrane) form of CD23 is consistently mitogenic for normal and transformed B lymphoblasts. Eur J Immunol. 1990 Mar;20(3):539–543. doi: 10.1002/eji.1830200312. [DOI] [PubMed] [Google Scholar]
  5. Conrad D. H. Fc epsilon RII/CD23: the low affinity receptor for IgE. Annu Rev Immunol. 1990;8:623–645. doi: 10.1146/annurev.iy.08.040190.003203. [DOI] [PubMed] [Google Scholar]
  6. Davis G. L., Balart L. A., Schiff E. R., Lindsay K., Bodenheimer H. C., Jr, Perrillo R. P., Carey W., Jacobson I. M., Payne J., Dienstag J. L. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med. 1989 Nov 30;321(22):1501–1506. doi: 10.1056/NEJM198911303212203. [DOI] [PubMed] [Google Scholar]
  7. Defrance T., Vanbervliet B., Durand I., Banchereau J. Human interleukin 4 down-regulates the surface expression of CD5 on normal and leukemic B cells. Eur J Immunol. 1989 Feb;19(2):293–299. doi: 10.1002/eji.1830190212. [DOI] [PubMed] [Google Scholar]
  8. Ghosh A. K., Dazzi H., Thatcher N., Moore M. Lack of correlation between peripheral blood lymphokine-activated killer (LAK) cell function and clinical response in patients with advanced malignant melanoma receiving recombinant interleukin 2. Int J Cancer. 1989 Mar 15;43(3):410–414. doi: 10.1002/ijc.2910430311. [DOI] [PubMed] [Google Scholar]
  9. Gordon J., Millsum M. J., Guy G. R., Ledbetter J. A. Resting B lymphocytes can be triggered directly through the CDw40 (Bp50) antigen. A comparison with IL-4-mediated signaling. J Immunol. 1988 Mar 1;140(5):1425–1430. [PubMed] [Google Scholar]
  10. Han X., Itoh K., Balch C. M., Pellis N. R. Recombinant interleukin 4 (RIL4) inhibits interleukin 2-induced activation of peripheral blood lymphocytes. Lymphokine Res. 1988 Fall;7(3):227–235. [PubMed] [Google Scholar]
  11. Hofman F. M., Brock M., Taylor C. R., Lyons B. IL-4 regulates differentiation and proliferation of human precursor B cells. J Immunol. 1988 Aug 15;141(4):1185–1190. [PubMed] [Google Scholar]
  12. Horohov D. W., Crim J. A., Smith P. L., Siegel J. P. IL-4 (B cell-stimulatory factor 1) regulates multiple aspects of influenza virus-specific cell-mediated immunity. J Immunol. 1988 Dec 15;141(12):4217–4223. [PubMed] [Google Scholar]
  13. Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hu-Li J., Shevach E. M., Mizuguchi J., Ohara J., Mosmann T., Paul W. E. B cell stimulatory factor 1 (interleukin 4) is a potent costimulant for normal resting T lymphocytes. J Exp Med. 1987 Jan 1;165(1):157–172. doi: 10.1084/jem.165.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jansen J. H., Wientjens G. J., Fibbe W. E., Willemze R., Kluin-Nelemans H. C. Inhibition of human macrophage colony formation by interleukin 4. J Exp Med. 1989 Aug 1;170(2):577–582. doi: 10.1084/jem.170.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kawakami Y., Custer M. C., Rosenberg S. A., Lotze M. T. IL-4 regulates IL-2 induction of lymphokine-activated killer activity from human lymphocytes. J Immunol. 1989 May 15;142(10):3452–3461. [PubMed] [Google Scholar]
  17. Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  18. Noelle R., Krammer P. H., Ohara J., Uhr J. W., Vitetta E. S. Increased expression of Ia antigens on resting B cells: an additional role for B-cell growth factor. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6149–6153. doi: 10.1073/pnas.81.19.6149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Park L. S., Friend D., Sassenfeld H. M., Urdal D. L. Characterization of the human B cell stimulatory factor 1 receptor. J Exp Med. 1987 Aug 1;166(2):476–488. doi: 10.1084/jem.166.2.476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Paul W. E. Interleukin-4: a prototypic immunoregulatory lymphokine. Blood. 1991 May 1;77(9):1859–1870. [PubMed] [Google Scholar]
  21. Rabin H., Hopkins R. F., 3rd, Ruscetti F. W., Neubauer R. H., Brown R. L., Kawakami T. G. Spontaneous release of a factor with properties of T cell growth factor from a continuous line of primate tumor T cells. J Immunol. 1981 Nov;127(5):1852–1856. [PubMed] [Google Scholar]
  22. Snapper C. M., Finkelman F. D., Paul W. E. Differential regulation of IgG1 and IgE synthesis by interleukin 4. J Exp Med. 1988 Jan 1;167(1):183–196. doi: 10.1084/jem.167.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Spits H., Yssel H., Takebe Y., Arai N., Yokota T., Lee F., Arai K., Banchereau J., de Vries J. E. Recombinant interleukin 4 promotes the growth of human T cells. J Immunol. 1987 Aug 15;139(4):1142–1147. [PubMed] [Google Scholar]
  24. Tepper R. I., Pattengale P. K., Leder P. Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell. 1989 May 5;57(3):503–512. doi: 10.1016/0092-8674(89)90925-2. [DOI] [PubMed] [Google Scholar]
  25. Treisman J., Higuchi C. M., Thompson J. A., Gillis S., Lindgren C. G., Kern D. E., Ridell S. R., Greenberg P. D., Fefer A. Enhancement by interleukin 4 of interleukin 2- or antibody-induced proliferation of lymphocytes from interleukin 2-treated cancer patients. Cancer Res. 1990 Feb 15;50(4):1160–1164. [PubMed] [Google Scholar]
  26. Widmer M. B., Acres R. B., Sassenfeld H. M., Grabstein K. H. Regulation of cytolytic cell populations from human peripheral blood by B cell stimulatory factor 1 (interleukin 4). J Exp Med. 1987 Nov 1;166(5):1447–1455. doi: 10.1084/jem.166.5.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zuber C. E., Galizzi J. P., Vallé A., Harada N., Howard M., Banchereau J. Interleukin 4 receptors on normal human B lymphocytes: characterization and regulation. Eur J Immunol. 1990 Mar;20(3):551–555. doi: 10.1002/eji.1830200314. [DOI] [PubMed] [Google Scholar]

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