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Drug Investigation

, Volume 3, Supplement 2, pp 71–74 | Cite as

Neutrophil Oxidative Responses

Cell-Directed and Scavenging Actions of the Anti-Inflammatory Drug Nimesulide
  • Franco Dallegri
  • L. Ottonello
  • F. Gatti
  • G. Guidi
Article

Summary

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.

Keywords

Chronic Obstructive Pulmonary Disease Scavenge Action Nimesulide HOCl Drug Invest 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Abramson SB, Weissmann G. The mechanisms of action of nonsteroidal anti-inflammatory drugs. Arthritis and Rheumatism 32: 1–9, 1989PubMedCrossRefGoogle Scholar
  2. Babior BM, Kipnes RS, Curnutte JJ. Biological defense mechanisms. The production by leukocytes of Superoxide, a potential bactericidal agent. Journal of Clinical Investigation 52: 741–744, 1970CrossRefGoogle Scholar
  3. Bevilacqua M, Vago T, Beretta A. Nimesulide as an inhibitor of Superoxide anion (O2 ) production by human polymorphonuclear leukocytes. In Genazzani et al. (Eds) Pain and reproduction, pp. 265–271, Parthenon Publishing Group, Carnforth, Lanes, UK, 1988Google Scholar
  4. Capsoni F, Venegoni E, Minonzio F, Ongari AM, Maresca V, et al. Inhibition of neutrophil oxidative metabolism by nimesulide. Agents and Actions 21: 121–129, 1987PubMedCrossRefGoogle Scholar
  5. Dallegri F, Goretti R, Ballestrero A, Ottonello L, Patrone F. Neutrophil-induced depletion of adenosine triphosphate in target cells: evidence for a hypoclorous acid-mediated process. Journal of Laboratory and Clinical Medicine 112: 765–772, 1988PubMedGoogle Scholar
  6. Dallegri F, Patrone F, Ballestrero A, Ottonello L, Ferrando F, et al. Inactivation of neutrophil-derived hypochlorous acid by nimesulide: a potential mechanism for the tissue protection during inflammation. International Journal of Tissue Reactions 12: 107–111, 1990PubMedGoogle Scholar
  7. Henson PM, Johnston RB. Tissue injury in inflammation. Oxidants, proteinases and cationic proteins. Journal of Clinical Investigation 79: 669–674, 1987 Leslie RGQ. Evaluation and improvement of a rapid microassay for measuring Superoxide anion production by phagocytes. Journal of Immunological Methods 103: 253–259, 1987CrossRefGoogle Scholar
  8. Styrt B. The role of phagocytes in non-infectious diseases. In Klempner et al. (Eds) Phagocytes and disease, pp. 145–169, Kluwer Academic Publisher, London, 1989CrossRefGoogle Scholar
  9. Weiss SJ. Tissue destruction by neutrophils. New England Journal of Medicine 320: 365–376, 1989PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • Franco Dallegri
    • 1
  • L. Ottonello
    • 1
  • F. Gatti
    • 2
  • G. Guidi
    • 2
  1. 1.First Medical Clinic, Department of Internal MedicineUniversity of Genoa Medical SchoolGenoaItaly
  2. 2.LPB Pharmaceutical InstituteMilanItaly

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