Skip to main content
SpringerLink
Log in

Tumour necrosis factor production in a rat airpouch model of inflammation: Role of eicosanoids

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

Abstract

TNF is a potent cytokine which can induce many of the pathological changes associated with inflammatory disease.In vitro studies have demonstrated that 5-lipoxygenase products promote the production of TNF by activated macrophages, suggesting that 5-lipoxygenase inhibitors may have therapeutic utility for the treatment of inflammatory conditions. A rat airpouch model of inflammation has been used to investigate the relationship between eicosanoid generation and TNF productionin vivo. Injection of zymosan into the airpouch caused a time-dependent stimulation of TNF production which preceded leukotriene generation by at least 30 minutes. Injection of LPS into the airpouch also stimulated TNF production but not leukotriene generation. The selective 5-lipoxygenase inhibitors, ICI207968, A64077 and BWA4C, and the 5-lipoxygenase translocation inhibitor MK886, decreased leukotriene generation but enhanced TNF production. Taken together, these results do not support a role for 5-lipoxygenase products in the regulation of TNF productionin vivo.

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. S. J. Hopkins and A. Meager,Cytokines in synovial fluid: II. The presence of tumour necrosis factor and interferon. Clin. Exp. Immunol.73, 88–92 (1988).

    PubMed  Google Scholar 

  2. D. E. Yocum, L. Esparza, S. Dubry, J. B. Benjamin, R. Volz and P. Scuderi,Characteristics of tumour necrosis factor production in rheumatoid arthritis. Cellular Immunol.122, 131–145 (1989).

    Article  Google Scholar 

  3. F. M. Brennan, D. Chantry, A. Jackson, R. Maini and M. Feldmann,Inhibitory effect of TNF-alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. The Lancet. July29, 244–247 (1989).

    Article  Google Scholar 

  4. J. Le and J. Vilcek,Tumour necrosis factor and interleukin-1: cytokines with multiple overlapping biological activities. Lab. Invest.56, 234–248 (1987).

    PubMed  Google Scholar 

  5. Y. Fong, K. J. Tracey, L. L. Moldawer, D. G. Hesse, K. B. Manogue, J. S. Kenney, A. T. Lee, G. C. Kuo, A. C. Allison, S. F. Lowry and A. Cerami,Antibodies to cachectin/tumour necrosis factor reduce interleukin-1 beta and interleukin-6 appearance during lethal bacteremia. J. Exp. Med.170, 1627–1633 (1989).

    Article  PubMed  Google Scholar 

  6. M. Rola-Pleszczynski and I. Lemaire,Leukotrienes augment interleukin-1 production by monocytes. J. Immunol.135, 3958–3961 (1985).

    PubMed  Google Scholar 

  7. L. Gagnon, L. G. Filion, C. Dubois and M. Rola-Pleszczynski,Leukotrienes and macrophage activation: augmented cytotoxic activity and enhanced production of interleukin-1, tumour necrosis factor and hydrogen peroxide production. Agents and Actions26, 141–147 (1989).

    PubMed  Google Scholar 

  8. S. L. Kunkel and S. W. Chensue,Arachidonic acid metabolites regulate interleukin-1 production. Biochem. Biophys. Res. Comm.128, 892–897 (1985).

    PubMed  Google Scholar 

  9. R. N. Spengler, M. L. Spengler, R. M. Strieter, D. G. Remick, J. W. Larrick and S. L. Kunkel,Modulation of tumour necrosis factor-alpha gene expression: Desensitization of prostaglandin E 2-induced suppression. J. Immunol.142, 4346–4350 (1989).

    PubMed  Google Scholar 

  10. W. E. Scales, S. W. Chensue, I. Otterness and S. L. Kunkel,Regulation of monokine gene expression: prostaglandin E 2 suppresses tumour necrosis factor but not interleukin-1 alpha or beta mRNA and cell-associated bioactivity. J. Leukocyte Biology45, 416–421 (1989).

    Google Scholar 

  11. J. C. W. Edwards, A. D. Sedgwick and D. A. Willoughby,The formation of a structure with features of synovial lining by subcutaneous injection of air: an in vivo tissue culture system. J. Pathol.134, 147–153 (1981).

    Article  PubMed  Google Scholar 

  12. S. J. Foster, P. Bruneau, E. R. H. Walker and R. M. McMillan,2-substitued indazolinones: orally active and selective 5-lipoxygenase inhibitors with anti-inflammatory activity. Br. J. Pharmacol.99, 113–118 (1990).

    PubMed  Google Scholar 

  13. R. A. Forder and F. Carey,Human 5-lipoxygenase: measurement by radioimmunoassay of LTB 4 in calcium ionophore stimulated blood. Prostaglandins28, 666 (1984).

    Article  Google Scholar 

  14. F. Carey and R. A. Forder,Radioimmunoassay of LTB 4 and 6-trans LTB4: analytical and pharmacological characterisation of immunoreactive LTB4 in ionophore stimulated human blood. Prostaglandins, Leukot Med.22, 57–70 (1986).

    Google Scholar 

  15. M. R. Ruff and G. E. Gifford,Purification and physicochemical characterisation of rabbit tumour necrosis factor. J. Immunol.125, 1617–1627 (1980).

    Google Scholar 

  16. S. J. Foster, M. E. McCormick, A. Howarth and D. Aked,Leukocyte recruitment in the subcutaneous sponge implant model of acute inflammation is not mediated by leukotriene B 4. Biochem. Pharmacol.35, 1709–1717 (1986).

    Article  PubMed  Google Scholar 

  17. J. E. Tateson, R. W. Randall, C. H. Reynolds, W. P. Jackson, P. Bhattacherjee, J. A. Salmon and L. G. Garland,Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acid biochemical assessment in vitro and in vivo. Br. J. Pharmacol.94, 528–539 (1988).

    PubMed  Google Scholar 

  18. J. Gillard et al.,L-663, 536 (MK886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid a novel, orally active leukotriene biosynthesis inhibitor. Can. J. Physiol. Pharmacol.67, 456–464 (1989).

    PubMed  Google Scholar 

  19. G. W. Carter, P. R. Young, D. H. Albert, J. B. Bouska, R. D. Dyer, R. L. Bell, J. B. Summers, D. W. Brooks, B. P. Gunn, P. Rubin and J. Kesterson,A-64077, a new potent orally active 5-lipoxygenase inhibitor. InNew trends in lipid mediator research, Vol. 3 (Eds. V. Zor, Z. Noar and A. Danon) (in press).

  20. C. M. Dubois, E. Bissonnette and M. Rola-Pleszczynski,Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumour necrosis factor: autoregulatory role of leukotriene B 4. Am. Rev. Respir. Dis.139, 1257–1264 (1989).

    PubMed  Google Scholar 

  21. C. A. Dinarello, I. Bishai, L. J. Rosenwasser and F. Coceani,The influence of lipoxygenase inhibitors on the in vitro production of human leukocyte pyrogen and lymphocyte activating factor (interleukin-1). Int. J. Immunopharmacol.6, 43–50 (1984).

    Article  PubMed  Google Scholar 

  22. S. Yoshino, W. J. Cromartie and J. H. Schwab,Inflammation induced by bacterial cell wall fragments in the rat airpouch: comparison of rat strains and measurement of arachidonic acid metabolites. Am. J. Pathol.121, 327–336 (1985).

    PubMed  Google Scholar 

  23. K. Chiba, H. Shirota, K. Katayama and I. Yamatsu,Interleukin-1-like activity in the exudate of air-pouch inflammation in rats, and its participation in granuloma formation. Agents and Actions27, 359–361 (1989).

    PubMed  Google Scholar 

  24. U. F. Schade, M. Ernst, M. Reinke, and D. T. Wolter,Lipoxygenase inhibitors suppress formation of tumour necrosis factor in vitro and in vivo. Biochem. Biophys. Res. Comm.159, 748–754 (1989).

    Article  PubMed  Google Scholar 

  25. U. F. Schade, H. Moll and E. Th. Rietschel,Metabolism of exogenous arachidonic acid by mouse peritoneal macrophages. Prostaglandins34, 401–412 (1987).

    Article  PubMed  Google Scholar 

  26. U. F. Schade, I. Burmeister and R. Engel,Increased 13-hydroxyoctadecadienoic acid content in lipopolysaccharide stimulated macrophages. Biochem. Biophys. Res. Comm.147, 695–700 (1987).

    Article  PubMed  Google Scholar 

  27. E. S. Wijelath and J. Watson,Influence of inhibitors of arachidonic acid cascade on interleukin-1 (IL-1) release. Biochem. Soc. Trans.15, 1138 (1987).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. ICI Pharmaceuticals, Bioscience 1, Mereside, Alderley Park, SK10 4TG, Macclesfield, Cheshire, UK

    M. L. Ferrándiz & S. J. Foster

Authors
  1. M. L. Ferrándiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. J. Foster
    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

Ferrándiz, M.L., Foster, S.J. Tumour necrosis factor production in a rat airpouch model of inflammation: Role of eicosanoids. Agents and Actions 32, 289–294 (1991). https://doi.org/10.1007/BF01980888

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01980888

Keywords

Search

Navigation