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Published on: June 8, 2012
Changes in cytokine and nitric oxide secretion by rat alveolar macrophages after oral administration of bacterial
E Broug-Holub1, J H Persoons, K Schornagel
1Department of Cell Biology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Abstract:
Oral administration of the bacterial immunomodulator Broncho-Vaxom (OM-85), a lysate of eight bacteria strains commonly causing respiratory disease, has been shown to enhance the host defence of the respiratory tract. In this study we examined the effect of orally administered (in vivo) OM-85 on stimulus-induced cytokine and nitric oxide secretion by rat alveolar macrophages in vitro. The results show that alveolar macrophages isolated from OM-85-treated rats secreted significantly more nitric oxide, tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta upon in vitro stimulation with lipopolysaccharide (LPS), whereas, in contrast, LPS-induced IL-6 secretion was significantly lower. The observed effects of in vivo OM-85 treatment on stimulus-induced cytokine secretion in vitro are not due to a direct effect of OM-85 on the cells, because in vitro incubation of alveolar macrophages with OM-85 did not result in altered activity, nor did direct intratracheal instillation of OM-85 in the lungs of rats result in altered alveolar macrophage activity in vitro. It is hypothesized that oral administration of OM-85 leads to priming of alveolar macrophages in such a way that immune responses are non-specifically enhanced upon stimulation. The therapeutic action of OM-85 may therefore result from an enhanced clearance of infectious bacteria from the respiratory tract due to increased alveolar macrophage activity.
Insights
Oral administration of Broncho-Vaxom (OM-85) primes alveolar macrophages, enhancing respiratory tract immune responses. This bacterial immunomodulator boosts nitric oxide and certain cytokine secretions, potentially improving bacterial clearance.
Area of Science:
- Immunology
- Pharmacology
- Respiratory Medicine
Background:
- Broncho-Vaxom (OM-85) is an oral bacterial lysate known to enhance respiratory tract host defense.
- Alveolar macrophages play a crucial role in respiratory tract immunity.
Purpose of the Study:
- To investigate the in vivo effects of orally administered OM-85 on the in vitro stimulus-induced cytokine and nitric oxide secretion by rat alveolar macrophages.
- To elucidate the mechanism by which OM-85 modulates alveolar macrophage activity.
Main Methods:
- Rats were orally administered OM-85.
- Alveolar macrophages were isolated from treated and control rats.
- Macrophages were stimulated in vitro with lipopolysaccharide (LPS).
- Nitric oxide, TNF-alpha, IL-1 beta, and IL-6 secretion levels were measured.
Main Results:
- OM-85 treatment significantly increased nitric oxide, TNF-alpha, and IL-1 beta secretion by LPS-stimulated alveolar macrophages.
- LPS-induced IL-6 secretion was significantly decreased in macrophages from OM-85-treated rats.
- Direct in vitro incubation or intratracheal instillation of OM-85 did not alter macrophage activity, suggesting an indirect priming effect.
Conclusions:
- Oral administration of OM-85 primes alveolar macrophages, leading to enhanced immune responses upon stimulation.
- This priming effect is hypothesized to contribute to the therapeutic action of OM-85 by improving bacterial clearance in the respiratory tract.
