Distinct effects of Broncho-Vaxom (OM-85 BV) on gp130 binding cytokines

Background-Broncho-Vaxom (OM-85 BV) is known to support respiratory tract r esistance 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 modulatio n of the host immune response, and it has been found to upregulate interfer on gamma (IFN-gamma) and interleukin (IL)-2, IL-6, and IL-8. These immunomo dulatory effects of the compound may explain its stimulation on T helper ce lls and natural killer cells. Following earlier findings that OM-85 BV indu ces the synthesis of IL-6, a study was undertaken to investigate its possib le effect on other gp130 binding cytokines including IL-11, IL-12, leukaemi a inhibitory factor (LIF), oncostatin M (OSM), and ciliary neutrophil facto r (CNTF). Its modulation of the corresponding receptors of the above mentio ned cytokines and of the signal transducer gp130 in human pulmonary fibrobl asts 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 lin ked immunosorbent assay kits. Cytokine receptors and gp130 proteins were de termined by Western blot analysis. Results-OM-85 BV increased the expression of IL-11 in human lung fibroblast s, but not in lymphocytes, in a dose and time dependent manner by maximal f ivefold within 20 hours. The compound inhibited serum induced IL-12 express ion 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 mu g/ml OM-85 BV while that of the IL-11 receptor was not altered. In peripheral blood lymphocytes LIF receptor a expression was downregulated in the presence of 10 mu g/ml OM-8 5 BV. At a concentration of 10 mu g/ml OM-85 BV enhanced gp130 gene transcr iption fivefold and increased gp130 protein accumulation in cell membranes by 2.5 times. Conclusion-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-alp ha further contributes to organ protection. With regard to gp130 mediated s ignalling of the investigated cytokines, OM-85 BV modifies the host immune response towards an increased sensitisation of cells to gp130 binding prote ins.