Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 Jun;40(6):1548–1551. doi: 10.1128/aac.40.6.1548

Inhibitory effect of erythromycin on interleukin 8 production by 1 alpha,25-dihydroxyvitamin D3-stimulated THP-1 cells.

T Fujii 1, J Kadota 1, T Morikawa 1, Y Matsubara 1, K Kawakami 1, K Iida 1, R Shirai 1, H Taniguchi 1, M Kaseda 1, S Kawamoto 1, S Kohno 1
PMCID: PMC163367  PMID: 8726037

Abstract

We have recently reported that long-term administration of erythromycin at a low dose reduced the number of neutrophils and concentrations of interleukin 8 (IL-8) in bronchoalveolar lavage fluid in patients with chronic lower respiratory tract disease. To investigate the mechanism of action of erythromycin, we evaluated its effect on IL-8 production in the 1 alpha,25-dihydroxyvitamin D3-stimulated human monocytic cell line THP-1. Erythromycin at a concentration of 10 micrograms/ml significantly reduced IL-8 production by THP-1 cells stimulated with lipopolysaccharide (10 ng/ml) and 1% normal human serum compared with the amount produced by untreated cells (untreated cells, 2,448 pg/ml; erythromycin-treated cells, 872 pg/ml). Our results suggest that erythromycin may impair IL-8 production by alveolar macrophages, ultimately reducing neutrophil accumulation in the airspace.

Full Text

The Full Text of this article is available as a PDF (261.0 KB).

Selected References

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

  1. Anderson R., Van Rensburg C. E., Jooné G., Lukey P. T. An in-vitro comparison of the intraphagocytic bioactivity of erythromycin and roxithromycin. J Antimicrob Chemother. 1987 Nov;20 (Suppl B):57–68. doi: 10.1093/jac/20.suppl_b.57. [DOI] [PubMed] [Google Scholar]
  2. Aoshiba K., Nagai A., Konno K. Erythromycin shortens neutrophil survival by accelerating apoptosis. Antimicrob Agents Chemother. 1995 Apr;39(4):872–877. doi: 10.1128/aac.39.4.872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fujii T., Kadota J., Kawakami K., Iida K., Shirai R., Kaseda M., Kawamoto S., Kohno S. Long term effect of erythromycin therapy in patients with chronic Pseudomonas aeruginosa infection. Thorax. 1995 Dec;50(12):1246–1252. doi: 10.1136/thx.50.12.1246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gallay P., Barras C., Tobias P. S., Calandra T., Glauser M. P., Heumann D. Lipopolysaccharide (LPS)-binding protein in human serum determines the tumor necrosis factor response of monocytes to LPS. J Infect Dis. 1994 Nov;170(5):1319–1322. doi: 10.1093/infdis/170.5.1319. [DOI] [PubMed] [Google Scholar]
  6. Homma H., Yamanaka A., Tanimoto S., Tamura M., Chijimatsu Y., Kira S., Izumi T. Diffuse panbronchiolitis. A disease of the transitional zone of the lung. Chest. 1983 Jan;83(1):63–69. doi: 10.1378/chest.83.1.63. [DOI] [PubMed] [Google Scholar]
  7. Ichikawa Y., Ninomiya H., Koga H., Tanaka M., Kinoshita M., Tokunaga N., Yano T., Oizumi K. Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients. Am Rev Respir Dis. 1992 Jul;146(1):196–203. doi: 10.1164/ajrccm/146.1.196. [DOI] [PubMed] [Google Scholar]
  8. Iwata M., Colby T. V., Kitaichi M. Diffuse panbronchiolitis: diagnosis and distinction from various pulmonary diseases with centrilobular interstitial foam cell accumulations. Hum Pathol. 1994 Apr;25(4):357–363. doi: 10.1016/0046-8177(94)90143-0. [DOI] [PubMed] [Google Scholar]
  9. Kadota J., Sakito O., Kohno S., Sawa H., Mukae H., Oda H., Kawakami K., Fukushima K., Hiratani K., Hara K. A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis. Am Rev Respir Dis. 1993 Jan;147(1):153–159. doi: 10.1164/ajrccm/147.1.153. [DOI] [PubMed] [Google Scholar]
  10. Khair O. A., Devalia J. L., Abdelaziz M. M., Sapsford R. J., Davies R. J. Effect of erythromycin on Haemophilus influenzae endotoxin-induced release of IL-6, IL-8 and sICAM-1 by cultured human bronchial epithelial cells. Eur Respir J. 1995 Sep;8(9):1451–1457. [PubMed] [Google Scholar]
  11. Kudoh S., Uetake T., Hagiwara K., Hirayama M., Hus L. H., Kimura H., Sugiyama Y. [Clinical effects of low-dose long-term erythromycin chemotherapy on diffuse panbronchiolitis]. Nihon Kyobu Shikkan Gakkai Zasshi. 1987 Jun;25(6):632–642. [PubMed] [Google Scholar]
  12. Lee C. T., Fein A. M., Lippmann M., Holtzman H., Kimbel P., Weinbaum G. Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome. N Engl J Med. 1981 Jan 22;304(4):192–196. doi: 10.1056/NEJM198101223040402. [DOI] [PubMed] [Google Scholar]
  13. Martin T. R., Rubenfeld G., Steinberg K. P., Hudson L. D., Raghu G., Moriarty A. M., Leturcq D. J., Tobias P. S., Ulevitch R. J. Endotoxin, endotoxin-binding protein, and soluble CD14 are present in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome. Chest. 1994 Mar;105(3 Suppl):55S–56S. doi: 10.1378/chest.105.3.55s. [DOI] [PubMed] [Google Scholar]
  14. McCord J. M., Fridovich I. The biology and pathology of oxygen radicals. Ann Intern Med. 1978 Jul;89(1):122–127. doi: 10.7326/0003-4819-89-1-122. [DOI] [PubMed] [Google Scholar]
  15. McElvaney N. G., Nakamura H., Birrer P., Hébert C. A., Wong W. L., Alphonso M., Baker J. B., Catalano M. A., Crystal R. G. Modulation of airway inflammation in cystic fibrosis. In vivo suppression of interleukin-8 levels on the respiratory epithelial surface by aerosolization of recombinant secretory leukoprotease inhibitor. J Clin Invest. 1992 Oct;90(4):1296–1301. doi: 10.1172/JCI115994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mitsuyama T., Tanaka T., Hidaka K., Abe M., Hara N. Inhibition by erythromycin of superoxide anion production by human polymorphonuclear leukocytes through the action of cyclic AMP-dependent protein kinase. Respiration. 1995;62(5):269–273. doi: 10.1159/000196461. [DOI] [PubMed] [Google Scholar]
  17. Mukae H., Hirota M., Kohno S., Komori K., Fukushima K., Hiratani K., Kadota J., Hara K. Elevation of tumor-associated carbohydrate antigens in patients with diffuse panbronchiolitis. Am Rev Respir Dis. 1993 Sep;148(3):744–751. doi: 10.1164/ajrccm/148.3.744. [DOI] [PubMed] [Google Scholar]
  18. Nagai H., Shishido H., Yoneda R., Yamaguchi E., Tamura A., Kurashima A. Long-term low-dose administration of erythromycin to patients with diffuse panbronchiolitis. Respiration. 1991;58(3-4):145–149. doi: 10.1159/000195915. [DOI] [PubMed] [Google Scholar]
  19. Oda H., Kadota J., Kohno S., Hara K. Leukotriene B4 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis. Chest. 1995 Jul;108(1):116–122. doi: 10.1378/chest.108.1.116. [DOI] [PubMed] [Google Scholar]
  20. Oishi K., Sonoda F., Kobayashi S., Iwagaki A., Nagatake T., Matsushima K., Matsumoto K. Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases. Infect Immun. 1994 Oct;62(10):4145–4152. doi: 10.1128/iai.62.10.4145-4152.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Prokesch R. C., Hand W. L. Antibiotic entry into human polymorphonuclear leukocytes. Antimicrob Agents Chemother. 1982 Mar;21(3):373–380. doi: 10.1128/aac.21.3.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Richman-Eisenstat J. B., Jorens P. G., Hébert C. A., Ueki I., Nadel J. A. Interleukin-8: an important chemoattractant in sputum of patients with chronic inflammatory airway diseases. Am J Physiol. 1993 Apr;264(4 Pt 1):L413–L418. doi: 10.1152/ajplung.1993.264.4.L413. [DOI] [PubMed] [Google Scholar]
  23. Sakito O., Kadota J., Kohno S., Abe K., Shirai R., Hara K. Interleukin 1 beta, tumor necrosis factor alpha, and interleukin 8 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis: a potential mechanism of macrolide therapy. Respiration. 1996;63(1):42–48. doi: 10.1159/000196514. [DOI] [PubMed] [Google Scholar]
  24. Schumann R. R., Leong S. R., Flaggs G. W., Gray P. W., Wright S. D., Mathison J. C., Tobias P. S., Ulevitch R. J. Structure and function of lipopolysaccharide binding protein. Science. 1990 Sep 21;249(4975):1429–1431. doi: 10.1126/science.2402637. [DOI] [PubMed] [Google Scholar]
  25. Tobias P. S., Soldau K., Kline L., Lee J. D., Kato K., Martin T. P., Ulevitch R. J. Cross-linking of lipopolysaccharide (LPS) to CD14 on THP-1 cells mediated by LPS-binding protein. J Immunol. 1993 Apr 1;150(7):3011–3021. [PubMed] [Google Scholar]
  26. Wright S. D., Ramos R. A., Tobias P. S., Ulevitch R. J., Mathison J. C. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990 Sep 21;249(4975):1431–1433. doi: 10.1126/science.1698311. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES