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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/97355
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.
Authors:
Scheid, Christof; Young, R; McDermott, R; Fitzsimmons, Lesley; Scarffe, J Howard; Stern, Peter L
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.
Affiliation:
CRC Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
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. 1994, 38 (2):119-26 Cancer Immunol. Immunother.
Journal:
Cancer immunology, Immunotherapy
Issue Date:
Feb-1994
URI:
http://hdl.handle.net/10541/97355
DOI:
10.1007/BF01526207
PubMed ID:
8306367
Type:
Article
Language:
en
ISSN:
0340-7004
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorScheid, Christofen
dc.contributor.authorYoung, Ren
dc.contributor.authorMcDermott, Ren
dc.contributor.authorFitzsimmons, Lesleyen
dc.contributor.authorScarffe, J Howarden
dc.contributor.authorStern, Peter Len
dc.date.accessioned2010-04-26T08:46:26Z-
dc.date.available2010-04-26T08:46:26Z-
dc.date.issued1994-02-
dc.identifier.citationImmune 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. 1994, 38 (2):119-26 Cancer Immunol. Immunother.en
dc.identifier.issn0340-7004-
dc.identifier.pmid8306367-
dc.identifier.doi10.1007/BF01526207-
dc.identifier.urihttp://hdl.handle.net/10541/97355-
dc.description.abstractInterleukin-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.en
dc.language.isoenen
dc.subjectColonic Canceren
dc.subjectPancreatic Canceren
dc.subject.meshAntibodies, Antinuclear-
dc.subject.meshC-Reactive Protein-
dc.subject.meshColonic Neoplasms-
dc.subject.meshHumans-
dc.subject.meshImmunoglobulin E-
dc.subject.meshInterleukin-6-
dc.subject.meshKiller Cells, Lymphokine-Activated-
dc.subject.meshKiller Cells, Natural-
dc.subject.meshLeukocyte Count-
dc.subject.meshLymphocyte Activation-
dc.subject.meshPancreatic Neoplasms-
dc.subject.meshRecombinant Proteins-
dc.titleImmune 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.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalCancer immunology, Immunotherapyen
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