Anti-inflammatory properties of a novel wound healing and immunomodulating agent, tetrachlorodecaoxygen complex (TCDO)

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Abstract
The first phase of the healing process is characterized by the development of an inflammatory reaction involving migration of inflammatory cells and release of inflammatory mediators. In a previous study, we have demonstrated that the water soluble tetrachlorodecaoxygen complex (TCDO), first synthetized to promote wound healing, inhibits polymorphonuclear (PMN) migration. The aim of the present study was to investigate the activity of TCDO on the progression of an acute non-specific inflammatory reaction, on the release of 6-keto-PGF1α and PGE2 and on PMN oxidative metabolism in the rat. Injected in the pleural cavity, TCDO (15 μmoles/rat) significantly decreased the number of exudative cells while 1.5 μmoles/rat inhibited PMN oxidative metabolismex vivo (assessed by chemiluminescent assay and measurement of O 2 − generation) after stimulation of the cells by opsonized zymosan. Similar observations were madein vitro after incubation of PMNs with various concentrations of TCDO (300 to 3 μM). The effect was dose-related and highly significant up to the concentration of 3 μM. In parallel, TCDO decreased the amounts of 6-keto-PGF1α and PGE2 in exudates harvested 1 hour after the intrapleural injection of isologous serum. Effects were significantly different from control levels, from 1.5 to 0.03 μmoles/rat for 6-keto-PGF1α and from 1.5 to 0.01 μmoles/rat for PGE2. This effect was observed when TCDO was injected at the same time or 1 hour before the isologous serum but not later. TCDO also inhibited LTB4 generationin vitro after PMN stimulation by calcium ionophore A23187, at concentrations up to 150 μM. The effects of TCDOin vivo andin vitro on rat PMN functions and inflammatory mediator release mimic certain activities of anti-inflammatory drugs. These properties may be beneficial in the very early stages of the wound healing process.

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