CHANGES IN CYTOKINE AND NITRIC-OXIDE SECRETION BY RAT ALVEOLAR MACROPHAGES AFTER ORAL-ADMINISTRATION OF BACTERIAL EXTRACTS

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 (i n vivo) OM-85 on stimulus-induced cytokine and nitric oxide secretion by rat alveolar macrophages in vitro. The results show that alveolar m acrophages isolated from OM-85-treated rats secreted significantly mor e 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 obse rved effects of in vivo OM-85 treatment on stimulus-induced cytokine s ecretion 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 n ot result in altered activity, nor did direct intratracheal instillati on 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 therapeu tic action of OM-85 may therefore result from an enhanced clearance of infectious bacteria from the respiratory tract due to increased alveo lar macrophage activity.