Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 May;112(1):111–116. doi: 10.1111/j.1476-5381.1994.tb13038.x

Drug modulation of antigen-induced paw oedema in guinea-pigs: effects of lipopolysaccharide, tumour necrosis factor and leucocyte depletion.

J I da Motta 1, F Q Cunha 1, B B Vargaftig 1, S H Ferreira 1
PMCID: PMC1910306  PMID: 8032630

Abstract

1. In guinea-pigs previously sensitized with ovalbumin, the intra-plantar administration of the antigen induced dose-dependent and sustained oedema. An intense infiltrate of neutrophils and eosinophils was observed at the peak of the oedema (4 h). 2. Oedema induced by ovalbumin at the doses of 50 or 200 micrograms/paw was not inhibited by antihistamines (meclizine and cetirizine), a PAF antagonist (BN 50730), a cyclo-oxygenase inhibitor (indomethacin), a lipoxygenase inhibitor (MK-886), a dual type lipo- and cyclo-oxygenase inhibitor (NDGA), a bradykinin antagonist (Hoe 140) or the combination of cetirizine, MK-886, indomethacin and BN 50730. These drugs did inhibit paw oedema induced by their specific agonists or by carrageenin. These results suggest that histamine, PAF, prostaglandins, leukotrienes or bradykinin are not important in the development of immune paw oedema in guinea-pigs. 3. Dexamethasone (10 mg kg-1) inhibited oedema induced by ovalbumin (50 or 200 micrograms/paw, P < 0.05). This effect apparently does not result from inhibition of arachidonate metabolism, since indomethacin, MK-886 and NDGA were without effect. 4. Oedema induced by ovalbumin (50 or 200 micrograms/paw) was also inhibited by azelastine. This effect was not due to the anti-histaminic property of azelastine since two other potent-antihistamines, meclizine and cetirizine, were ineffective. 5. Intravenous injection of lipopolysaccharide (LPS) dose-dependently inhibited the oedema induced by ovalbumin (200 micrograms/paw). This effect could not be attributed to hypotension or leucopenia since the maximal dose applied (81 micrograms kg-1) did not induce significant changes in the blood pressure or in the white blood cell levels of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
111

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Besedovsky H., del Rey A., Sorkin E., Dinarello C. A. Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science. 1986 Aug 8;233(4764):652–654. doi: 10.1126/science.3014662. [DOI] [PubMed] [Google Scholar]
  2. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  3. Claman H. N. Corticosteroids and lymphoid cells. N Engl J Med. 1972 Aug 24;287(8):388–397. doi: 10.1056/NEJM197208242870806. [DOI] [PubMed] [Google Scholar]
  4. Cortijo J., Ortiz J. L., Sanz C., Sarría B., Pascual R., Perpiñ M., Esplugues J., Morcillo E. J. Modification by indomethacin of airway contractile responses in normal and sensitized guinea-pigs. Eur J Pharmacol. 1989 Mar 29;162(3):467–473. doi: 10.1016/0014-2999(89)90337-3. [DOI] [PubMed] [Google Scholar]
  5. Cunha F. Q., Cacini A. T., Ferreira S. H. Inhibition of the release of a neutrophil chemotactic factor from macrophages partially explains the anti-inflammatory action of glucocorticoids. Agents Actions. 1986 Jan;17(3-4):314–317. doi: 10.1007/BF01982632. [DOI] [PubMed] [Google Scholar]
  6. Daffonchio L., Lees I. W., Payne A. N., Whittle B. J. Pharmacological modulation of bronchial anaphylaxis induced by aerosol challenge in anaesthetized guinea-pigs. Br J Pharmacol. 1987 Jul;91(3):701–708. doi: 10.1111/j.1476-5381.1987.tb11265.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Desquand S., Lefort J., Dumarey C., Vargaftig B. B. The booster injection of antigen during active sensitization of guinea-pig modifies the anti-anaphylactic activity of the PAF antagonist WEB 2086. Br J Pharmacol. 1990 Jun;100(2):217–222. doi: 10.1111/j.1476-5381.1990.tb15785.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dinarello C. A. The proinflammatory cytokines interleukin-1 and tumor necrosis factor and treatment of the septic shock syndrome. J Infect Dis. 1991 Jun;163(6):1177–1184. doi: 10.1093/infdis/163.6.1177. [DOI] [PubMed] [Google Scholar]
  9. Faccioli L. H., Souza G. E., Cunha F. Q., Poole S., Ferreira S. H. Recombinant interleukin-1 and tumor necrosis factor induce neutrophil migration "in vivo" by indirect mechanisms. Agents Actions. 1990 Jun;30(3-4):344–349. doi: 10.1007/BF01966298. [DOI] [PubMed] [Google Scholar]
  10. Flower R. J. Eleventh Gaddum memorial lecture. Lipocortin and the mechanism of action of the glucocorticoids. Br J Pharmacol. 1988 Aug;94(4):987–1015. doi: 10.1111/j.1476-5381.1988.tb11614.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Iwama T., Nagai H., Tsuruoka N., Koda A. Effect of murine recombinant interleukin-5 on bronchial reactivity in guinea-pigs. Clin Exp Allergy. 1993 Jan;23(1):32–38. doi: 10.1111/j.1365-2222.1993.tb02481.x. [DOI] [PubMed] [Google Scholar]
  12. Kay A. B., Roberts E. M., Jones D. G. Tissue inactivation of slow reacting substance of anaphylaxis. Immunology. 1976 Jan;30(1):83–87. [PMC free article] [PubMed] [Google Scholar]
  13. Lellouch-Tubiana A., Lefort J., Simon M. T., Pfister A., Vargaftig B. B. Eosinophil recruitment into guinea pig lungs after PAF-acether and allergen administration. Modulation by prostacyclin, platelet depletion, and selective antagonists. Am Rev Respir Dis. 1988 Apr;137(4):948–954. doi: 10.1164/ajrccm/137.4.948. [DOI] [PubMed] [Google Scholar]
  14. Lima M. C., Martins M. A., Perez S. A., Silva P. M., Cordeiro R. S., Vargaftig B. B. Effect of azelastine on platelet-activating factor and antigen-induced pleurisy in rats. Eur J Pharmacol. 1991 May 17;197(2-3):201–207. doi: 10.1016/0014-2999(91)90522-r. [DOI] [PubMed] [Google Scholar]
  15. Magnussen H. The inhibitory effect of azelastine and ketotifen on histamine-induced bronchoconstriction in asthmatic patients. Chest. 1987 Jun;91(6):855–858. doi: 10.1378/chest.91.6.855. [DOI] [PubMed] [Google Scholar]
  16. Otsuka Y., Nagano K., Nagano K., Hori K., Oh-ishi J., Hayashi H., Watanabe N., Niitsu Y. Inhibition of neutrophil migration by tumor necrosis factor. Ex vivo and in vivo studies in comparison with in vitro effect. J Immunol. 1990 Oct 15;145(8):2639–2643. [PubMed] [Google Scholar]
  17. Pretolani M., Lefort J., Venco C., Perrisoud D., Vargaftig B. B. Inhibition by azelastine of the effects of platelet-activating factor in lungs from actively sensitised guinea-pigs. Eur J Pharmacol. 1992 Jun 5;216(2):141–147. doi: 10.1016/0014-2999(92)90354-7. [DOI] [PubMed] [Google Scholar]
  18. Rand T. H., Silberstein D. S., Kornfeld H., Weller P. F. Human eosinophils express functional interleukin 2 receptors. J Clin Invest. 1991 Sep;88(3):825–832. doi: 10.1172/JCI115383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ribeiro R. A., Flores C. A., Cunha F. Q., Ferreira S. H. IL-8 causes in vivo neutrophil migration by a cell-dependent mechanism. Immunology. 1991 Aug;73(4):472–477. [PMC free article] [PubMed] [Google Scholar]
  20. Rocha N. P., Ferreira S. H. Restoration by levamisole of endotoxin-inhibited neutrophil migration, oedema and increased vascular permeability induced by carrageenin. Eur J Pharmacol. 1986 Mar 11;122(1):87–92. doi: 10.1016/0014-2999(86)90162-7. [DOI] [PubMed] [Google Scholar]
  21. Rosenbaum J. T., Hartiala K. T., Webster R. O., Howes E. L., Jr, Goldstein I. M. Antiinflammatory effects of endotoxin. Inhibition of rabbit polymorphonuclear leukocyte responses to complement (C5)-derived peptides in vivo and in vitro. Am J Pathol. 1983 Dec;113(3):291–299. [PMC free article] [PubMed] [Google Scholar]
  22. Salyer J. L., Bohnsack J. F., Knape W. A., Shigeoka A. O., Ashwood E. R., Hill H. R. Mechanisms of tumor necrosis factor-alpha alteration of PMN adhesion and migration. Am J Pathol. 1990 Apr;136(4):831–841. [PMC free article] [PubMed] [Google Scholar]
  23. Sanjar S., Aoki S., Kristersson A., Smith D., Morley J. Antigen challenge induces pulmonary airway eosinophil accumulation and airway hyperreactivity in sensitized guinea-pigs: the effect of anti-asthma drugs. Br J Pharmacol. 1990 Apr;99(4):679–686. doi: 10.1111/j.1476-5381.1990.tb12989.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Smith D., Burrows L., Westwick J. Interleukin-8--a mediator of inflammatory lung disease? Adv Exp Med Biol. 1991;305:119–126. doi: 10.1007/978-1-4684-6009-4_14. [DOI] [PubMed] [Google Scholar]
  25. Tracey K. J., Fong Y., Hesse D. G., Manogue K. R., Lee A. T., Kuo G. C., Lowry S. F., Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987 Dec 17;330(6149):662–664. doi: 10.1038/330662a0. [DOI] [PubMed] [Google Scholar]
  26. Vannier E., Lefort J., Lellouch-Tubiana A., Terlain B., Vargaftig B. B. Lipopolysaccharide from Escherichia coli reduces antigen-induced bronchoconstriction in actively sensitized guinea pigs. J Clin Invest. 1991 Jun;87(6):1936–1944. doi: 10.1172/JCI115219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wasserman S. I., Goetzl E. J., Austen K. F. Inactivation of slow reacting substance of anaphylaxis by human eosinophil arylsulfatase. J Immunol. 1975 Feb;114(2 Pt 1):645–649. [PubMed] [Google Scholar]
  28. Weg V. B., Watson M. L., Cordeiro R. S., Williams T. J. Histamine, leukotriene D4 and platelet-activating factor in guinea pig passive cutaneous anaphylaxis. Eur J Pharmacol. 1991 Nov 5;204(2):157–163. doi: 10.1016/0014-2999(91)90700-z. [DOI] [PubMed] [Google Scholar]
  29. de Souza G. E., Ferreira S. H. Blockade by antimacrophage serum of the migration of PMN neutrophils into the inflamed peritoneal cavity. Agents Actions. 1985 Oct;17(1):97–103. doi: 10.1007/BF01966691. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES