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The intratracheal administration of endotoxin: X. Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo

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Abstract

Intratracheal instillation of endotoxin (LPS) causes acute pulmonary inflammation characterized by the accumulation of plasma proteins and leukocytes within the pulmonary airways. The synthetic glucocorticoid dexamethasone 1) inhibits the LPS-initiated vascular leak of plasma proteins into the airspace, 2) inhibits the LPS-initiated emigration of neutrophils and lymphocytes into the airspace in a dose-dependent fashion, and 3) inhibits LPS-initiated mRNA and/or bronchoalveolar lavage protein expression of cytokines (TNF, IL-1 and IL-6) and chemokines (MIP-lα, MIP-2 and MCP-1). In conclusion, dexamethasone inhibits both the vascular and cellular aspects of acute inflammation by downregulation of a broad spectrum of inflammatory cytokines and chemokines.

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References

  1. Cotran, R. S., V. Kumar, andS. L. Robbins. 1989.Pathologic Basis of Diseases. Philadelphia, PA, W. B. Saunders, pp. 40–63.

    Google Scholar 

  2. Ulich, T. R., L. R.Watson, S.Yin, K.Guo, P.Wang, H.Thang, and J. delCastillo. The intratracheal administration of endotoxin and cytokines: I. Characterization of LPS-induced IL-1 and TNF mRNA expression and the LPS-, IL-1-, and TNF-induced inflammatory infiltrate.Am. J. Pathol. 138:1485–1496.

  3. Ulich, T. R., S. Yin, D. G. Remick, D. Russel, S. P. Eisenberg, andT. Kohno. 1993. Intratracheal administration of endotoxin and cytokines: IV. The soluble tumor necrosis factor receptor type I inhibits acute inflammation.Am. J. Pathol.142:1335–1338.

    PubMed  Google Scholar 

  4. Ulich, T. R., E. S. Yi, S. Yin, C. Smith, andD. G. Remick. 1994. Intratracheal administration of endotoxin and cytokines: VII. The soluble interleukin-1 receptor and the soluble tumor necrosis factor receptor II (p80) inhibit acute inflammation.Clin. Immunol. Immunopathol. 72:137–140.

    PubMed  Google Scholar 

  5. Ulich, T. R., S. Yin, K. Guo, J. del Castillo, S. P. Eisenberg, andR. C. Thompson. 1991. The intratracheal administration of endotoxin and cytokines: III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation.Am. J. Pathol. 138:521–524.

    PubMed  Google Scholar 

  6. Ulich, T. R., S. C.Howard, D. G.Remick, A.Wittwer, E. S.Yi, S.Yin, K.Guo, J. K.Welply, and J. H.Williams. Intratracheal administration of endotoxin and cytokines: VI, LPS induces CINC chemotactic peptide expression and antiserum to CINC inhibits acute inflammation.Am. J. Physiol. (Lung Cell Mol Physiol), in press.

  7. Huang, S., J. D. Paulauskis, J. J. Godleski, L. Kobzik. 1992. Expression of macrophage inflammatory protein-2 and KC mRNA in pulmonary inflammation.Am. J. Pathol 141:981–988.

    PubMed  Google Scholar 

  8. Ulich, T. R., S. C. Howard, D. G. Remick, E. S. Yi, T. Collins, K. Guo, S. Yin, J. L. Keene, J. J. Schmuke, C. N. Steinger, J. K. Welply, andJ. H. Williams. 1994. Intratracheal administration of endotoxin and cytokines: VIII. LPS induces E-selectin expression. Anti-E selectin and soluble E-selectin inhibit acute inflammation.Infl 18:389–394.

    Google Scholar 

  9. Lowry, O. H., N. J. Rosebrough, A. L. Farr, andR. J. Randall. 1951. Protein measurement with the folin phenol reagent.J. Biol. Chem. 193:265–275.

    PubMed  Google Scholar 

  10. Nadziejko, C., andJ. Chen. 1994. Increased elastase inhibitory capacity of lung lavage fluid following acute ozone exposure: role of serum transudation.Inhal. Tox. 6:57–65.

    Google Scholar 

  11. Fujita, J., N. L. Nelson, D. M. Daughton, C. A. Dobry, J. R. Spurzen, S. Irino, S. Rennard. 1990. Evaluation of elastase and antielastase balance in patient with chronic bronchitis and pulmonary emphysema.Am. Rev. Respir. Dis. 142:57–62.

    PubMed  Google Scholar 

  12. Ulich, T. R., B. Irwin, D. G. Remick, andG. N. Davastellis. 1990. Endotoxin-induced cytokine gene expression in vivo: II. Regulation of TNF and IL-1 expression and suppression.Am. J. Pathol. 137:1137–1145.

    Google Scholar 

  13. Ulich, T. R., K. Guo, D. G. Remick, J. del Castillo, S. Yin. 1991. Endotoxin-induced cytokine gene expression in vivo. III. IL-6 mRNA and serum protein expression and the in vivo hematologic effects of IL-6.J. Immunol. 146:2316–2323.

    PubMed  Google Scholar 

  14. Northermann, W., T. A. Bracial, N. Hatton, F. Lee, andG. H. Fey. 1990. Structure of the rat IL-6 gene and its expression in macrophage-derived cellsJ. Biol. Chem. 264:160–172.

    Google Scholar 

  15. Chirgwin, J., A. Przbyla, andR. MacDonald. 1979. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.Biochemistry 18:5294–5299.

    PubMed  Google Scholar 

  16. Yi, E. S., T. R. Ulich. Endotoxin, interleukin-1, and tumor necrosis factor cause neutrophildependent microvascular leakage in postcapillary venules. Am. J. Pathol. 1992,140:659–663.

    PubMed  Google Scholar 

  17. Hocking, D. C., P. G. Phillips, T. J. Ferro, andA. Johnson. 1990. Mechanisms of pulmonary edema induced by TNF.Circ. Res. 67:68–77.

    PubMed  Google Scholar 

  18. Stephens, K. E., A. Ishizaka, Z. H. Wu, J. W. Larrick, T. A. Raffin. 1988. Granulocyte depletion prevents TNF-mediated acute lung injury in guinea pigs.Am. Rev. Respir. Dis. 138:1300–1307.

    PubMed  Google Scholar 

  19. Matsushima, K., C. G.Larsen, G. C.DuBois, J. J.Oppenheim. Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line.J Exp. Med. 169:1484–1490.

  20. Jiang, Y., D. I. Beller, G. Frendl, D. T. Graves. 1992. Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes.J Immunol. 148:2423–2428.

    PubMed  Google Scholar 

  21. Brieland, J. K., M. L. Jones, S. J. Clarke, J. B. Baker, J. S. Warren, J. C. Fantone. 1992. Effect of acute inflammatory lung injury on the expression of monocyte chemoattractant protein-1 (MCP-1) in rat pulmonary alveolar macrophages.Am. J. Respir. Cell. Mol. Biol. 7:134–139.

    PubMed  Google Scholar 

  22. Koch, A. E., S. L. Kunkel, L. A. Harlow, B. Johnson, H. L. Evanoff, G. K. Haines, M. D. Burdick, R. M. Pope, R. M. Strieter. 1992. Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis.J. Clin. Invest. 90:772–779.

    PubMed  Google Scholar 

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Yi, E.S., Remick, D.G., Lim, Y. et al. The intratracheal administration of endotoxin: X. Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo. Inflammation 20, 165–175 (1996). https://doi.org/10.1007/BF01487403

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