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Br J Cancer. 1992 July; 66(1): 204–210.
PMCID: PMC1977892

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

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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  • 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]
  • Broxmeyer HE, Lu L, Cooper S, Tushinski R, Mochizuki D, Rubin BY, Gillis S, Williams DE. 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]
  • Cabrillat H, Galizzi JP, 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. [PubMed]
  • Cairns JA, 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. [PubMed]
  • Conrad DH. Fc epsilon RII/CD23: the low affinity receptor for IgE. Annu Rev Immunol. 1990;8:623–645. [PubMed]
  • Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC, Jr, Perrillo RP, Carey W, Jacobson IM, Payne J, Dienstag JL, et al. 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. [PubMed]
  • 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. [PubMed]
  • Ghosh AK, 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. [PubMed]
  • Gordon J, Millsum MJ, Guy GR, Ledbetter JA. 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]
  • Han X, Itoh K, Balch CM, Pellis NR. Recombinant interleukin 4 (RIL4) inhibits interleukin 2-induced activation of peripheral blood lymphocytes. Lymphokine Res. 1988 Fall;7(3):227–235. [PubMed]
  • Hofman FM, Brock M, Taylor CR, Lyons B. IL-4 regulates differentiation and proliferation of human precursor B cells. J Immunol. 1988 Aug 15;141(4):1185–1190. [PubMed]
  • Horohov DW, Crim JA, Smith PL, Siegel JP. 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]
  • Howard M, Farrar J, Hilfiker M, Johnson B, Takatsu K, Hamaoka T, Paul WE. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. [PMC free article] [PubMed]
  • Hu-Li J, Shevach EM, Mizuguchi J, Ohara J, Mosmann T, Paul WE. 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. [PMC free article] [PubMed]
  • Jansen JH, Wientjens GJ, Fibbe WE, Willemze R, Kluin-Nelemans HC. Inhibition of human macrophage colony formation by interleukin 4. J Exp Med. 1989 Aug 1;170(2):577–582. [PMC free article] [PubMed]
  • Kawakami Y, Custer MC, Rosenberg SA, Lotze MT. IL-4 regulates IL-2 induction of lymphokine-activated killer activity from human lymphocytes. J Immunol. 1989 May 15;142(10):3452–3461. [PubMed]
  • Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. [PubMed]
  • Noelle R, Krammer PH, Ohara J, Uhr JW, Vitetta ES. 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. [PubMed]
  • Park LS, Friend D, Sassenfeld HM, Urdal DL. Characterization of the human B cell stimulatory factor 1 receptor. J Exp Med. 1987 Aug 1;166(2):476–488. [PMC free article] [PubMed]
  • Paul WE. Interleukin-4: a prototypic immunoregulatory lymphokine. Blood. 1991 May 1;77(9):1859–1870. [PubMed]
  • Rabin H, Hopkins RF, 3rd, Ruscetti FW, Neubauer RH, Brown RL, Kawakami TG. 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]
  • Snapper CM, Finkelman FD, Paul WE. Differential regulation of IgG1 and IgE synthesis by interleukin 4. J Exp Med. 1988 Jan 1;167(1):183–196. [PMC free article] [PubMed]
  • Spits H, Yssel H, Takebe Y, Arai N, Yokota T, Lee F, Arai K, Banchereau J, de Vries JE. Recombinant interleukin 4 promotes the growth of human T cells. J Immunol. 1987 Aug 15;139(4):1142–1147. [PubMed]
  • Tepper RI, Pattengale PK, Leder P. Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell. 1989 May 5;57(3):503–512. [PubMed]
  • Treisman J, Higuchi CM, Thompson JA, Gillis S, Lindgren CG, Kern DE, Ridell SR, Greenberg PD, 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]
  • Widmer MB, Acres RB, Sassenfeld HM, Grabstein KH. 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. [PMC free article] [PubMed]
  • Zuber CE, Galizzi JP, 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. [PubMed]

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