title: 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.
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 microgram/kg and 20 micrograms/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 fixed Staphylococcus 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 micrograms/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 acute-phase 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.
authors.affiliation: CRC Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
authors.forename: C
authors.initials: C
authors.lastname: Scheid
authors.forename: R
authors.initials: R
authors.lastname: Young
authors.forename: R
authors.initials: R
authors.lastname: McDermott
authors.forename: L
authors.initials: L
authors.lastname: Fitzsimmons
authors.forename: J H
authors.initials: JH
authors.lastname: Scarffe
authors.forename: P L
authors.initials: PL
authors.lastname: Stern
mesh_terms: D000974:Antibodies, Antinuclear / Q000032:analysis; D002097:C-Reactive Protein / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D015850:Interleukin-6 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology; D011994:Recombinant Proteins
chemical_list: D000974:Antibodies, Antinuclear; D015850:Interleukin-6; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D002097:C-Reactive Protein