Skip to main content
SpringerLink
Log in

In vivo modulation of leukotaxis by non-steroidal anti-inflammatory drugs

  • Immunosuppression and Inflammation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

Since non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for inhibition of inflammation, anin vivo assay for leukotaxis would be of use in comparing the biological activity effects of the agents. Here, the effects of 4 different NSAIDs onin vivo leukocyte accumulation was determined by quantitatingN-formyl-methionyl-leucylphenylalanine induced leukotaxis in the rabbit anterior eye chamber. New Zealand white female rabbits were treated for three days with the following regimens: ibuprofen or aspirin, 0.1, 1.0, 10.0 or 100.0 mg/kg/day, indomethacin or flurbiprofen, 0.01, 0.1, 1.0, or 10.0 mg/kg/day. Indomethacin and flurbiprofen significantly reduced leukotaxis in a dose of 10.0 mg/kg/day. Aspirin was associated with a weak inhibition of leukotaxis. Ibuprofen had biphasic effects, 1.0 mg/kg/day potentiated and 10 mg/kg/day inhibited leukotaxis, whereas leukocyte accumulation was uneffected by a high dose (100.0 mg/kg/day). These results suggest that modulation of leukotaxis by NSAIDs may reflect a differential dose-response sensitivity of lipoxygenase and cycloxygenase pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. F.N. Rowland, M.J. Donovan, M. Lindsay, W.I. Weiss, J. O'Rourke andD.L. Kreutzer,Demonstration of inflammatory mediator-induced inflammation and endothelial cell damage in the anterior segment of the eye, Am. J. Path.110, 1 (1983).

    PubMed  Google Scholar 

  2. P. Bhattacherjee, B. Hammond, J.A. Salmon, R. Stepney andK.E. Eakins,Chemotactic response to some arachidonic acid lipoxygenase products in the rabbit eye, Eur. J. Pharmac.73, 21 (1981).

    Article  Google Scholar 

  3. T. Shimanuki, R.M. Nakamura andG.S. diZerega,Modulation of leukotaxis by ibuprofen: a quantitative determination in vivo, Inflammation (in review).

  4. A.W. Ford-Hutchinson, M.A. Bray andM.J.H. Smith,Lipoxygenase products and the polymorphonuclear leukocyte, Agents and Actions10, 548 (1980).

    PubMed  Google Scholar 

  5. C.V. Wedmore andT.J. Williams,Control of vascular permeability by polymorphonuclear leukocytes in inflammation, Nature, Lond.289, 646 (1981).

    Google Scholar 

  6. R.M.J. Palmer, R.J. Stepney, G.A. Higgs andK.E. Eakins,Chemokinetic activity of arachidonic acid lipoxygenase products on leukocytes of different species, Prostaglandins20, 411 (1980).

    PubMed  Google Scholar 

  7. S.E. Dahlen, J. Bjork, P. Hedqvist, K.E. Arfors, S. Hammarstrom, J.A. Lindgren andB. Samuelsson,Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response, Proc. natn. Acad. Sci. USA78, 3887 (1981).

    Google Scholar 

  8. H.J. Showell, R.J. Freer, S.H. Zigmond, E. Schiffmann, S. Aswanikumar, B. Corcoran andE.L. Becker,The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal enzyme secretion for neutrophils, J. exp. Med.143, 1154 (1976).

    Google Scholar 

  9. B.J. Bormann, C.K. Huang, W.M. Mackin andE.L. Becker,Receptor-mediated activation of a phospholipase A 2 in rabbit neutrophil plasma membrane, Proc. natn. Acad. Sci USA81, 767 (1984).

    Google Scholar 

  10. F. Hirata, B.A. Corcoran, K. Venkatasubramanian, E. Schiffmann andJ. Axelrod,Chemoattractants stimulate degradation of methylated phospholipids and release of arachidonic acid in rabbit leukocytes, Proc. natn. Acad. Sci. USA76, 2640 (1979).

    Google Scholar 

  11. W. Jubiz, O. Radmark, C. Malmstern, G. Hansson, J.A. Lindgren, J. Palmblad, A.M. Uden andB. Samuelsson,A novel leukotriene produced by stimulation of leukocytes with formylmethionylleucylphenylalanine, J. biol. Chem.257, 6106 (1982).

    PubMed  Google Scholar 

  12. G.M. Bokoch andP.W. Reed,Stimulation of arachidonic acid metabolism in the polymorphonuclear leukocyte by an N-formylated peptide, J. biol. Chem.255, 10223 (1980).

    PubMed  Google Scholar 

  13. J.R. Walker, M.J.K. Smith andA.W. Ford-Hutchinson,Anti-inflammatory drugs, prostaglandins and leukocyte migration, Agents and Actions6, 602 (1976).

    PubMed  Google Scholar 

  14. G.A. Higgs, K.E. Eakins, K.G. Mugridge, S. Moncada andJ.R. Vane,The effects of non-steroid anti-inflammatory drugs on leukocyte migration in carrageenin-induced inflammation, Eur. J. Pharmac.66, 81 (1980).

    Article  Google Scholar 

  15. J. Palmblad, C.L. Malmstern, A.M. Uden, O. Radmark, L. Engstedt andB. Samuelsson,Leukotriene B 4 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence, Blood58, 658 (1981).

    PubMed  Google Scholar 

  16. H.J. Showell, P.H. Naccache, R.I. Shaafi andE.L. Becker,Inhibition of rabbit neutrophil lysosomal enzyme secretion, non-stimulated and chemotactic factor stimulated locomotion by nordihydroguaiaretic acid, Life Sci.27, 421 (1980).

    Article  PubMed  Google Scholar 

  17. R.F. Myers andM.I. Siegel,Differential effects of anti-inflammatory drugs on lipoxygenase and cyclooxygenase activities of neutrophils from a reverse passive arthus reaction, Biochem. biophys. Res. Commun.112, 586 (1983).

    Article  PubMed  Google Scholar 

  18. R.W. Randall, K.E. Eakins, G.A. Higgs J.A. Salmon andJ.E. Tateson,Inhibition of arachidonic acid cyclo-oxygenase and lipoxygenase activities of leukocytes by indomethacin and compound BW 755C, Agents and Actions10, 553 (1980).

    PubMed  Google Scholar 

  19. K.A. Brown andA.J. Collins,Action of nonsteroidal, anti-inflammatory drugs on human and rat peripheral leukocyte migration in vitro, Ann, rheum. Dis.36, 239 (1977).

    Google Scholar 

  20. M.A. Bray, A.W. Ford-Hutchinson, M.E. Sphipley andM.J.H. Smith,Calcium ionophere A23187 induces release of chemokinetic and aggregating factors from polymorphonuclear leukocytes, Br. J. Pharmac.71, 507 (1980).

    Google Scholar 

  21. E. Magliulo, R. Benzi-Cipelli, A. Lago, M. Azzini, E. Magni, S. Gallico andG. Sacchetti,Inhibiting effect on non-steroidal anti-inflammatory drugs on the chemotaxis of human leukocytes in vitro, Intl. J. Clin. Pharmacol.15, 417 (1977).

    Google Scholar 

  22. S. Spisani, G. Vanzini andS. Traniello,Inhibition of human leukocytes locomotion by anti-inflammatory drugs, Experientia35, 803 (1979).

    PubMed  Google Scholar 

  23. M.J.H. Smith andJ.R. Walker,The effects of some antirheumatic drugs on an in vitro model of human polymorphonuclear leukocyte chemokinesis, Br. J. Pharmac.69, 473 (1980).

    Google Scholar 

  24. N. Ackerman, S. Martinez, T. Thieme andA. Mirkovich,Relationship between adherence, chemotaxis and the accumulation of rat polymorphonuclear leukocytes at an inflammatory site, J. Pharmac. exp. Ther.221, 701 (1982).

    Google Scholar 

  25. E. McCall andL.J.F. Youlten,The effect of indomethacin and depletion of complement on cell migration and prostaglandin levels in carrageenin-induced air bled inflammation, Br. J. Pharmac.52, 452 (1974).

    Google Scholar 

  26. M.R. MacAdams, S.B. Pek andW.E.M. Lands,The effect of flurbiprofen, a potent inhibitor of prostaglandin synthesis, on insulin and glucagon release from isolated rat pancreas, Endocrinology114, 1364 (1984).

    PubMed  Google Scholar 

  27. E.A. Ham, D. D. Soderman, M.E. Zanetti, H.W. Dougherty, E. Mcauley andF.A. Kuehl,Inhibition by prostaglandins of leukotriene B 4 release from activated neutrophils, Proc. natn. Acad. Sci. USA80, 4349 (1983).

    Google Scholar 

  28. P.C. Bragt andI.L. Bonta,Indomethacin inhibits the in vivo formation of the lipoxygenase product HETE (12-hydroxy-5,8,10.14-eicosatetraenoic acid) during granulomatous inflammation in the rat, J, Pharm. Pharmac.32, 143 (1980).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Livingston Reproductive Biology Laboratory, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California

    Robert M. Nakamura & Gere S. diZerega M.D.

  2. The Second Department of Surgery, Yamagata School of Medicine, Yamagata, Japan

    Takao Shimanuki

Authors
  1. Takao Shimanuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert M. Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gere S. diZerega M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shimanuki, T., Nakamura, R.M. & diZerega, G.S. In vivo modulation of leukotaxis by non-steroidal anti-inflammatory drugs. Agents and Actions 17, 80–83 (1985). https://doi.org/10.1007/BF01966687

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01966687

Keywords

Search

Navigation