Immune function of patients receiving recombinant human interleukin-6 (IL-6) in a phase I clinical study: Induction of C-reactive protein and IgE and inhibition of natural killer and lymphokine-activated killer cell activity |
| |
Authors: | C. Scheid R. Young R. McDermott L. Fitzsimmons J. H. Scarffe P. L. Stern |
| |
Affiliation: | (1) CRC Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, M20 9BX Manchester, UK;(2) Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, M20 9BX Manchester, UK |
| |
Abstract: | Interleukin-6 (IL-6) is a cytokine that acts on a variety of cell types, including myeloid progenitor cells and B and T lymphocytes. It has been found to activate cytotoxic T cells and natural killer (NK) cells and to induce T-cell-mediated antitumour effects in animal models. In a phase I clinical trial of recombinant human IL-6, 20 patients with advanced cancer were entered to receive daily subcutaneous injections of IL-6 over 7 days followed by a 2-week observation period and another 4 weeks of daily IL-6 injections. Doses varied between 0.5 g/kg and 20 g/ kg body weight and immune functions were monitored throughout. At all dose levels IL-6 administration led to a marked increase in serum levels of C-reactive protein and a moderate rise in complement factor C3. The proportions of CD4, CD8 or HLA-DR lymphocytes in peripheral blood did not alter with IL-6 treatment nor did the in vitro proliferation of peripheral blood mononuclear cells induced by either phytohaemagglutinin, pokeweed mitogen or fixedStaphylococcus aureus. By contrast, NK cell activity, lymphokine-activated killer (LAK) cell activity and proliferation induced by in vitro culture with interleukin-2 (IL-2) were suppressed at doses exceeding 2.5 g/kg. Serum IgE levels were consistently elevated over the IL-6 dose range but IgM, IgG and IgA levels were unaffected. In summary there is a dose-dependent induction of acutephase proteins by in vivo IL-6 treatment. At higher IL-6 doses there is a suppressive effect on NK and LAK activity measured in vitro. IL-6 may thus be useful in combination cytokine therapies that seek to suppress LAK and favour cytotoxic T lymphocyte responses. The rise in IgE levels in response to IL-6 was unexpected and suggests a more pivotal role than previously known for the control of IgE production; this could include IgE-related diseases.Supported by a Mildred Scheel Research-Fellowship from the Deutsche Krebshilfe |
| |
Keywords: | Interleukin-2 Interleukin-6 NK activity LAK activity IgE Cancer |
本文献已被 SpringerLink 等数据库收录! |
|