Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1995 Oct;102(1):78–84. doi: 10.1111/j.1365-2249.1995.tb06639.x

Inhibition of tumour necrosis factor-alpha (TNF-alpha) release from mast cells by the anti-inflammatory drugs, sodium cromoglycate and nedocromil sodium.

E Y Bissonnette 1, J A Enciso 1, A D Befus 1
PMCID: PMC1553325  PMID: 7554404

Abstract

TNF-alpha is a cytokine thought to be involved in the pathogenesis of asthma and in several other inflammatory conditions. Given recent evidence that mast cells (MC) are an important source of TNF-alpha, we investigated the effects of two anti-inflammatory drugs, nedocromil sodium (NED) and sodium cromoglycate (SCG), on rat MC-derived TNF-alpha. We established that at least 2 h pretreatment with NED or SCG followed by washing was required to inhibit TNF-alpha-dependent cytotoxicity by rat peritoneal MC (PMC). A maximum inhibition of TNF-alpha occurred after 6 h treatment. The inhibitory effect of NED and SCG (10(-5)-10(-3)M) was concentration-dependent (20-37% for NED and 16-37% for SCG). The time-course analysis and the use of cycloheximide, an inhibitor of protein synthesis, provided strong evidence that new protein synthesis by the MC is required for this inhibitory effect. Furthermore, 24 h treatment with 1 mM NED inhibited the levels of mRNA for TNF-alpha by 59-83%. In addition to the effect on TNF-alpha-dependent cytotoxicity by MC, 20 min pretreatment with 10(-4) M NED and SCG inhibited antigen-stimulated TNF-alpha release (6h) by 42% and 48%, respectively. Interestingly, the functionally distinct intestinal mucosal MC (IMMC) is unresponsive to these drugs with regard to histamine secretion. However, as with PMC, 2h pretreatment with NED or SCG inhibited TNF-alpha-dependent cytotoxicity by IMMC. These effects may be important in the action of these drugs in vivo in the late phase reaction in asthma or other inflammatory conditions.

Full text

PDF
80

Images in this article

82Fig. 6
on p.82

Selected References

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

  1. Ahmed S. A., Gogal R. M., Jr, Walsh J. E. A new rapid and simple non-radioactive assay to monitor and determine the proliferation of lymphocytes: an alternative to [3H]thymidine incorporation assay. J Immunol Methods. 1994 Apr 15;170(2):211–224. doi: 10.1016/0022-1759(94)90396-4. [DOI] [PubMed] [Google Scholar]
  2. Arai K. I., Lee F., Miyajima A., Miyatake S., Arai N., Yokota T. Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem. 1990;59:783–836. doi: 10.1146/annurev.bi.59.070190.004031. [DOI] [PubMed] [Google Scholar]
  3. Baraldi E., Santuz P., Magagnin G., Filippone M., Zacchello F. Effect of disodium cromoglycate on ventilation and gas exchange during exercise in asthmatic children with a postexertion FEV1 fall less than 15 percent. Chest. 1994 Oct;106(4):1083–1088. doi: 10.1378/chest.106.4.1083. [DOI] [PubMed] [Google Scholar]
  4. Barnes P. J. Cytokines as mediators of chronic asthma. Am J Respir Crit Care Med. 1994 Nov;150(5 Pt 2):S42–S49. doi: 10.1164/ajrccm/150.5_Pt_2.S42. [DOI] [PubMed] [Google Scholar]
  5. Befus A. D., Johnston N., Bienenstock J. Nippostrongylus brasiliensis: mast cells and histamine levels in tissues of infected and normal rats. Exp Parasitol. 1979 Aug;48(1):1–8. doi: 10.1016/0014-4894(79)90048-1. [DOI] [PubMed] [Google Scholar]
  6. Benyon R. C., Bissonnette E. Y., Befus A. D. Tumor necrosis factor-alpha dependent cytotoxicity of human skin mast cells is enhanced by anti-IgE antibodies. J Immunol. 1991 Oct 1;147(7):2253–2258. [PubMed] [Google Scholar]
  7. Bissonnette E. Y., Befus A. D. Inhibition of mast cell-mediated cytotoxicity by IFN-alpha/beta and -gamma. J Immunol. 1990 Nov 15;145(10):3385–3390. [PubMed] [Google Scholar]
  8. Bradding P., Roberts J. A., Britten K. M., Montefort S., Djukanovic R., Mueller R., Heusser C. H., Howarth P. H., Holgate S. T. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol. 1994 May;10(5):471–480. doi: 10.1165/ajrcmb.10.5.8179909. [DOI] [PubMed] [Google Scholar]
  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  10. Church M. K., Warner J. O. Sodium cromoglycate and related drugs. Clin Allergy. 1985 Jul;15(4):311–320. doi: 10.1111/j.1365-2222.1985.tb02998.x. [DOI] [PubMed] [Google Scholar]
  11. Crimi E., Brusasco V., Crimi P. Effect of nedocromil sodium on the late asthmatic reaction to bronchial antigen challenge. J Allergy Clin Immunol. 1989 May;83(5):985–990. doi: 10.1016/0091-6749(89)90116-4. [DOI] [PubMed] [Google Scholar]
  12. Edwards A. M. Sodium cromoglycate (Intal) as an anti-inflammatory agent for the treatment of chronic asthma. Clin Exp Allergy. 1994 Jul;24(7):612–623. doi: 10.1111/j.1365-2222.1994.tb00964.x. [DOI] [PubMed] [Google Scholar]
  13. Gonzalez J. P., Brogden R. N. Nedocromil sodium. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of reversible obstructive airways disease. Drugs. 1987 Nov;34(5):560–577. doi: 10.2165/00003495-198734050-00004. [DOI] [PubMed] [Google Scholar]
  14. Gordon J. R., Galli S. J. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature. 1990 Jul 19;346(6281):274–276. doi: 10.1038/346274a0. [DOI] [PubMed] [Google Scholar]
  15. Gordon J. R., Galli S. J. Release of both preformed and newly synthesized tumor necrosis factor alpha (TNF-alpha)/cachectin by mouse mast cells stimulated via the Fc epsilon RI. A mechanism for the sustained action of mast cell-derived TNF-alpha during IgE-dependent biological responses. J Exp Med. 1991 Jul 1;174(1):103–107. doi: 10.1084/jem.174.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kay A. B. Asthma and inflammation. J Allergy Clin Immunol. 1991 May;87(5):893–910. doi: 10.1016/0091-6749(91)90408-g. [DOI] [PubMed] [Google Scholar]
  17. Kips J. C., Tavernier J. H., Joos G. F., Peleman R. A., Pauwels R. A. The potential role of tumour necrosis factor alpha in asthma. Clin Exp Allergy. 1993 Apr;23(4):247–250. doi: 10.1111/j.1365-2222.1993.tb00317.x. [DOI] [PubMed] [Google Scholar]
  18. Lee T. D., Shanahan F., Miller H. R., Bienenstock J., Befus A. D. Intestinal mucosal mast cells: isolation from rat lamina propria and purification using unit gravity velocity sedimentation. Immunology. 1985 Aug;55(4):721–728. [PMC free article] [PubMed] [Google Scholar]
  19. Marone G. Control mechanisms of mediator release in human basophils and mast cells. Immunol Invest. 1988 Nov-Dec;17(8-9):707–745. doi: 10.3109/08820138809089019. [DOI] [PubMed] [Google Scholar]
  20. Ohno I., Ohkawara Y., Yamauchi K., Tanno Y., Takishima T. Production of tumor necrosis factor with IgE receptor triggering from sensitized lung tissue. Am J Respir Cell Mol Biol. 1990 Oct;3(4):285–289. doi: 10.1165/ajrcmb/3.4.285. [DOI] [PubMed] [Google Scholar]
  21. Okayama Y., Benyon R. C., Rees P. H., Lowman M. A., Hillier K., Church M. K. Inhibition profiles of sodium cromoglycate and nedocromil sodium on mediator release from mast cells of human skin, lung, tonsil, adenoid and intestine. Clin Exp Allergy. 1992 Mar;22(3):401–409. doi: 10.1111/j.1365-2222.1992.tb03102.x. [DOI] [PubMed] [Google Scholar]
  22. Old L. J. Tumor necrosis factor (TNF). Science. 1985 Nov 8;230(4726):630–632. doi: 10.1126/science.2413547. [DOI] [PubMed] [Google Scholar]
  23. Pearce F. L., Befus A. D., Bienenstock J. Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells. J Allergy Clin Immunol. 1984 Jun;73(6):819–823. doi: 10.1016/0091-6749(84)90453-6. [DOI] [PubMed] [Google Scholar]
  24. Pearce F. L., Befus A. D., Gauldie J., Bienenstock J. Mucosal mast cells. II. Effects of anti-allergic compounds on histamine secretion by isolated intestinal mast cells. J Immunol. 1982 Jun;128(6):2481–2486. [PubMed] [Google Scholar]
  25. Pennica D., Hayflick J. S., Bringman T. S., Palladino M. A., Goeddel D. V. Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6060–6064. doi: 10.1073/pnas.82.18.6060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pross H. F., Baines M. G., Rubin P., Shragge P., Patterson M. S. Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity. J Clin Immunol. 1981 Jan;1(1):51–63. doi: 10.1007/BF00915477. [DOI] [PubMed] [Google Scholar]
  27. Ruhno J., Denburg J., Dolovich J. Intranasal nedocromil sodium in the treatment of ragweed-allergic rhinitis. J Allergy Clin Immunol. 1988 Mar;81(3):570–574. [PubMed] [Google Scholar]
  28. Sette A., Adorini L., Marubini E., Doria G. A microcomputer program for probit analysis of interleukin-2 (IL-2) titration data. J Immunol Methods. 1986 Feb 12;86(2):265–277. doi: 10.1016/0022-1759(86)90463-1. [DOI] [PubMed] [Google Scholar]
  29. Shanahan F., Lee T. D., Bienenstock J., Befus A. D. Mast cell heterogeneity: effect of anti-allergic compounds on neuropeptide-induced histamine release. Int Arch Allergy Appl Immunol. 1986;80(4):424–426. doi: 10.1159/000234092. [DOI] [PubMed] [Google Scholar]
  30. Shanahan F., Lee T. D., Bienenstock J., Befus A. D. The influence of endorphins on peritoneal and mucosal mast cell secretion. J Allergy Clin Immunol. 1984 Oct;74(4 Pt 1):499–504. doi: 10.1016/0091-6749(84)90385-3. [DOI] [PubMed] [Google Scholar]
  31. Strieter R. M., Kunkel S. L., Bone R. C. Role of tumor necrosis factor-alpha in disease states and inflammation. Crit Care Med. 1993 Oct;21(10 Suppl):S447–S463. doi: 10.1097/00003246-199310001-00006. [DOI] [PubMed] [Google Scholar]
  32. Tosi M. F., Stark J. M., Smith C. W., Hamedani A., Gruenert D. C., Infeld M. D. Induction of ICAM-1 expression on human airway epithelial cells by inflammatory cytokines: effects on neutrophil-epithelial cell adhesion. Am J Respir Cell Mol Biol. 1992 Aug;7(2):214–221. doi: 10.1165/ajrcmb/7.2.214. [DOI] [PubMed] [Google Scholar]
  33. Wershil B. K., Furuta G. T., Lavigne J. A., Choudhury A. R., Wang Z. S., Galli S. J. Dexamethasone or cyclosporin A suppress mast cell-leukocyte cytokine cascades. Multiple mechanisms of inhibition of IgE- and mast cell-dependent cutaneous inflammation in the mouse. J Immunol. 1995 Feb 1;154(3):1391–1398. [PubMed] [Google Scholar]
  34. Wershil B. K., Wang Z. S., Gordon J. R., Galli S. J. Recruitment of neutrophils during IgE-dependent cutaneous late phase reactions in the mouse is mast cell-dependent. Partial inhibition of the reaction with antiserum against tumor necrosis factor-alpha. J Clin Invest. 1991 Feb;87(2):446–453. doi: 10.1172/JCI115016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. de Benedictis F. M., Tuteri G., Bertotto A., Bruni L., Vaccaro R. Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children. J Allergy Clin Immunol. 1994 Oct;94(4):684–688. doi: 10.1016/0091-6749(94)90175-9. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES