Neutrophil Oxidative Responses
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Nimesulide affects neutrophil behaviour during inflammatory reactions at 2 steps of the cell response. It reduces oxidant production during neutrophil interaction with chemotactic factors (cell-directed action) without affecting cell locomotory capacity, and during phagocytosis (cell-directed action) without limiting neutrophil ingestive efficiency. In addition, nimesulide acts as an inactivator of the hypochlorous acid generated during the phagocytic process (scavenging action). The drug-concentration threshold for the scavenging action of nimesulide (10−5 mol/L) appears to be lower than that for the cell-directed actions (> 5 × 10−5 mol/L). As the cell-directed actions result in reduction but not complete suppression of the cell-responding capacity (downregulation), neutrophils can be expected to maintain their ability to handle microorganisms, as suggested by the lack of infection during nimesulide treatment. On the other hand, the control of neutrophil oxidative potential, detected at drug concentrations achievable in plasma after oral administration, is likely to contribute to the anti-inflammatory activity of the drug by limiting the extracellular availability of toxic oxidants.
KeywordsChronic Obstructive Pulmonary Disease Scavenge Action Nimesulide HOCl Drug Invest
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