In vivo expression of monokine and inducible nitric oxide synthase in experimentally induced pulmonary granulomatous inflammation. Evidence for sequential production of interleukin-1, inducible nitric oxide synthase, and tumor necrosis factor.

The present study examined the temporal pattern and localization of interleukin-1, tumor necrosis factor-alpha, and inducible nitric oxide synthase expression in lung tissue undergoing foreign body granuloma formation. Pulmonary granulomas were induced by the intratracheal injection of dextran beads into genetically high granuloma responder, carrying Bcgs (BALB/c), and low responder, carrying Bcgr (C3H/HeJ and DBA/2), mice. There was a pattern of sequential expression of these molecules in BALB/c mice. Thus, interleukin-1 alpha and inducible nitric oxide synthase were induced mostly in the cells accumulated around the beads and also in some bronchiolar epithelial cells during the early phase (1 to 3 days), whereas tumor necrosis factor-alpha was induced in the cells around the beads at the later resolution phase (3 to 7 days). By contrast, in low responder mice, an increase in the expression of interleukin-1 alpha and inducible nitric oxide synthase was detected in lung macrophages as well as in alveolar cells and bronchiolar epithelial cells on day 1, but that of tumor necrosis factor-alpha was not detected throughout the period. These results together with our previous findings on cytokine activity in granuloma extract suggest that interleukin-1 and nitric oxide produced by recruited macrophages may take part in the early, macrophage-dependent phase of granuloma formation whereas tumor necrosis factor-alpha may be more crucial as a mediator responsible for the difference in innate resistance or susceptibility to granuloma formation.

Immunomodulatory action of propolis. V. Anticomplementary activity of a water-soluble derivative.

The effect of a water-soluble derivative (WSD) of propolis on the classical pathway (CP) and the alternative (AP) complement activity has been investigated. The in vitro experiments show that WSD inhibits both pathways and the effect depends on the source of complement. The suppression of complement-mediated haemolysis proves to be time- and temperature-related. High WSD concentrations cause direct damage of the target erythrocytes. The estimation of C3-residual activity indicates that the preparation diminishes C3 functional activity.

Immunomodulatory action of propolis. VI. Influence of a water soluble derivative on complement activity in vivo.

The water soluble derivative (WSD) of propolis in a dose of 150 mg/kg was administered intravenously (i.v.), intraperitoneally (i.p.) and orally (p.o.) to mice. The alteration of serum alternative pathway (AP) complement level was observed. The WSD also influenced the process of acute inflammation provoked by zymosan in mice. The effect was strongly dependent on the route of WSD administration.