Distinct effects of Broncho-Vaxom (OM-85 BV) on gp130 binding cytokines.
BACKGROUND
Broncho-Vaxom (OM-85 BV) is known to support respiratory tract resistance to bacterial infections. In vivo and in vitro studies in animals and humans have shown that the action of the drug is based on the modulation of the host immune response, and it has been found to upregulate interferon gamma (IFN-gamma) and interleukin (IL)-2, IL-6, and IL-8. These immunomodulatory effects of the compound may explain its stimulation on T helper cells and natural killer cells. Following earlier findings that OM-85 BV induces the synthesis of IL-6, a study was undertaken to investigate its possible effect on other gp130 binding cytokines including IL-11, IL-12, leukaemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neutrophil factor (CNTF). Its modulation of the corresponding receptors of the above mentioned cytokines and of the signal transducer gp130 in human pulmonary fibroblasts and peripheral blood lymphocytes was also studied.


METHODS
Transcription of cytokines was assessed by Northern blot analysis. Secretion of cytokines was analysed using commercially available enzyme linked immunosorbent assay kits. Cytokine receptors and gp130 proteins were determined by Western blot analysis.


RESULTS
OM-85 BV increased the expression of IL-11 in human lung fibroblasts, but not in lymphocytes, in a dose and time dependent manner by maximal fivefold within 20 hours. The compound inhibited serum induced IL-12 expression in peripheral blood lymphocytes but did not induce OSM, LIF, or CNTF at any concentration. In lung fibroblasts the expression of the IL-6 receptor was enhanced fourfold at a concentration of 10 microg/ml OM-85 BV while that of the IL-11 receptor was not altered. In peripheral blood lymphocytes LIF receptor alpha expression was downregulated in the presence of 10 microg/ml OM-85 BV. At a concentration of 10 microg/ml OM-85 BV enhanced gp130 gene transcription fivefold and increased gp130 protein accumulation in cell membranes by 2.5 times.


CONCLUSIONS
In vitro OM-85 BV exerts immunomodulatory action via modulation of the signal transducer gp130 and gp130 binding cytokines. The increase of IL-6 and IL-11 may explain enhanced T and B cell activity, immunoglobulin synthesis, and IgM to IgG switch. Suppression of IL-12 and LIF receptor-alpha further contributes to organ protection. With regard to gp130 mediated signalling of the investigated cytokines, OM-85 BV modifies the host immune response towards an increased sensitisation of cells to gp130 binding proteins.
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Division of Pneumology, Departments of Research and Internal Medicine, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000704:Analysis of Variance; D015703:Antigens, CD / Q000187:drug effects* / Q000378:metabolism; D001419:Bacteria; D002457:Cell Extracts; D002460:Cell Line; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology*; D017370:Interleukin-11 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000187:drug effects / Q000378:metabolism*; D000095983:Bacterial Lysates
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D002457:Cell Extracts; D050822:Cytokine Receptor gp130; D016207:Cytokines; D007369:Interferon Inducers; D017370:Interleukin-11; D018664:Interleukin-12; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; C030259:Broncho-Vaxom; D000095983:Bacterial Lysates; C494199:IL6ST protein, human