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Effect of an immunomodulating agent, RU 414740, on polymorphonuclear responsiveness after burn injury
M Roch-Arveiller1, J Fontagne, A el Abbouyi
1CNRS URA 595-Pharmacologie and Biochimie A Hôpital Cochin, Paris, France.
Abstract:
An impairment of polymorphonuclear leukocyte (PMN) functions has been described following burn trauma. It was thus of interest to investigate the effect of RU 41740, an agent known to stimulate these cells, on rat PMN functions after burn injury. In the present study the responsiveness to classical stimuli of PMN from untreated burned rats was approximately 40% lower than healthy control values. In vitro treatment with RU 41740 increased oxidative metabolism of PMNs from burned and healthy rats. The effect was dose-related but was most striking in the case of PMNs from healthy rats. Significant differences were obtained with concentrations higher than 1 micrograms/ml for healthy rats but only 10 micrograms/ml for burned rats. In vivo treatment with RU 41740 also led to an enhancement of PMN oxidative metabolism on both burned and healthy rats. The maximal effective dose was 10 mg/kg/day in both cases. In contrast, 25 and 50 mg/kg/day doses inhibited PMN oxidative metabolism.
Insights
Burn injury impairs polymorphonuclear leukocyte (PMN) function. RU 41740, a PMN stimulant, enhanced oxidative metabolism in PMNs from both burned and healthy rats in vitro and in vivo.
Area of Science:
- Immunology
- Trauma Research
Background:
- Burn trauma is known to impair polymorphonuclear leukocyte (PMN) functions.
- Investigating agents that can restore or enhance PMN function post-burn is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the effect of RU 41740, a known PMN stimulant, on rat PMN functions following burn injury.
- To assess both in vitro and in vivo effects of RU 41740 on PMN oxidative metabolism in burned and healthy rats.
Main Methods:
- Burned and healthy rats were used to assess PMN function.
- In vitro and in vivo experiments were conducted using RU 41740 at varying concentrations and doses.
- Oxidative metabolism of PMNs was measured as an indicator of function.
Main Results:
- PMN responsiveness to stimuli was reduced by approximately 40% in untreated burned rats compared to controls.
- RU 41740 treatment increased PMN oxidative metabolism in both healthy and burned rats, with a dose-dependent effect.
- In vitro, higher RU 41740 concentrations were needed for burned rats (10 µg/ml) than healthy rats (1 µg/ml) to show significant effects.
- In vivo, 10 mg/kg/day of RU 41740 was the maximal effective dose for enhancing PMN oxidative metabolism in both groups, while higher doses (25-50 mg/kg/day) showed inhibitory effects.
Conclusions:
- RU 41740 demonstrates potential in enhancing impaired PMN oxidative metabolism following burn injury.
- Both in vitro and in vivo administration of RU 41740 can modulate PMN function, suggesting therapeutic possibilities.
- Optimal dosing is critical, as higher concentrations/doses of RU 41740 can inhibit PMN oxidative metabolism.
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