Skip to main content
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1998;7(1):41–47. doi: 10.1080/09629359891379

Interleukin-5 modulates interleukin-8 secretion in eosinophilic inflammation.

L H Faccioli 1, A I Medeiros 1, A Malheiro 1, R C Pietro 1, A Januário 1, B B Vargaftig 1
PMCID: PMC1781822  PMID: 9839698

Abstract

Serum and BALF (bronchoalveolar lavage fluid) IL-8 levels and serum levels were investigated in Toxocara canis infected guinea-pigs and the role of IL-5 as a modulator of cytokine secretion was studied. Serum levels increased early in infected animals, exceeding control levels 4 h after infection, peaked between days 6 and 18, and continued to exceed control levels after 48 days of infection. Serum and BALF IL-8 levels showed the same profile as blood eosinophilia, increasing 6 days post-infection and peaking between days 18 and 24. Treatment of infected animals with anti-IL-5 Ab suppressed eosinophilia with a parallel increase in blood IL-8 levels, whereas no change was found in levels. To support our in vivo observation we carried out experiments in vitro using guinea-pig LPS-stimulated adherent peritoneal cells which release large amounts of IL-8 into the supernatants. When rIL-5 was added to LPS-stimulated cells, 65% inhibition of IL-8 release into the supernatants was observed. Pre-incubation of cells with anti-IL-5 Ab prevented the inhibition of IL-8 release into the supernatants induced by rIL-5. Our results demonstrate for the first time that TNF-alpha and IL-8 are released concomitant with or after IL-5 in the eosinophilic inflammation induced by T. canis. Moreover, in addition to showing that IL-5 is fundamental for the induction of blood eosinophilia, the present results suggest that this cytokine may play a new biological role by acting as modulator of IL-8 secretion.

Full Text

The Full Text of this article is available as a PDF (206.7 KB).

Selected References

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

  1. BEAVER P. C., SNYDER C. H., CARRERA G. M., DENT J. H., LAFFERTY J. W. Chronic eosinophilia due to visceral larva migrans; report of three cases. Pediatrics. 1952 Jan;9(1):7–19. [PubMed] [Google Scholar]
  2. Becker S., Quay J., Soukup J. Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages. J Immunol. 1991 Dec 15;147(12):4307–4312. [PubMed] [Google Scholar]
  3. Braun R. K., Franchini M., Erard F., Rihs S., De Vries I. J., Blaser K., Hansel T. T., Walker C. Human peripheral blood eosinophils produce and release interleukin-8 on stimulation with calcium ionophore. Eur J Immunol. 1993 Apr;23(4):956–960. doi: 10.1002/eji.1830230429. [DOI] [PubMed] [Google Scholar]
  4. Calandra T., Baumgartner J. D., Grau G. E., Wu M. M., Lambert P. H., Schellekens J., Verhoef J., Glauser M. P. Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group. J Infect Dis. 1990 May;161(5):982–987. doi: 10.1093/infdis/161.5.982. [DOI] [PubMed] [Google Scholar]
  5. Cannon J. G., Tompkins R. G., Gelfand J. A., Michie H. R., Stanford G. G., van der Meer J. W., Endres S., Lonnemann G., Corsetti J., Chernow B. Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis. 1990 Jan;161(1):79–84. doi: 10.1093/infdis/161.1.79. [DOI] [PubMed] [Google Scholar]
  6. Cembrzynska-Nowak M., Szklarz E., Inglot A. D., Teodorczyk-Injeyan J. A. Elevated release of tumor necrosis factor-alpha and interferon-gamma by bronchoalveolar leukocytes from patients with bronchial asthma. Am Rev Respir Dis. 1993 Feb;147(2):291–295. doi: 10.1164/ajrccm/147.2.291. [DOI] [PubMed] [Google Scholar]
  7. Chensue S. W., Otterness I. G., Higashi G. I., Forsch C. S., Kunkel S. L. Monokine production by hypersensitivity (Schistosoma mansoni egg) and foreign body (Sephadex bead)-type granuloma macrophages. Evidence for sequential production of IL-1 and tumor necrosis factor. J Immunol. 1989 Feb 15;142(4):1281–1286. [PubMed] [Google Scholar]
  8. Coffman R. L., Seymour B. W., Hudak S., Jackson J., Rennick D. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1989 Jul 21;245(4915):308–310. doi: 10.1126/science.2787531. [DOI] [PubMed] [Google Scholar]
  9. Collins P. D., Weg V. B., Faccioli L. H., Watson M. L., Moqbel R., Williams T. J. Eosinophil accumulation induced by human interleukin-8 in the guinea-pig in vivo. Immunology. 1993 Jun;79(2):312–318. [PMC free article] [PubMed] [Google Scholar]
  10. Coyle A. J., Erard F., Bertrand C., Walti S., Pircher H., Le Gros G. Virus-specific CD8+ cells can switch to interleukin 5 production and induce airway eosinophilia. J Exp Med. 1995 Mar 1;181(3):1229–1233. doi: 10.1084/jem.181.3.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Coëffier E., Joseph D., Vargaftig B. B. Role of interleukin-5 in enhanced migration of eosinophils from airways of immunized guinea-pigs. Br J Pharmacol. 1994 Nov;113(3):749–756. doi: 10.1111/j.1476-5381.1994.tb17057.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eum S. Y., Hailé S., Lefort J., Huerre M., Vargaftig B. B. Eosinophil recruitment into the respiratory epithelium following antigenic challenge in hyper-IgE mice is accompanied by interleukin 5-dependent bronchial hyperresponsiveness. Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12290–12294. doi: 10.1073/pnas.92.26.12290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Figueiredo F., Alves L. M., Silva C. L. Tumour necrosis factor production in vivo and in vitro in response to Paracoccidioides brasiliensis and the cell wall fractions thereof. Clin Exp Immunol. 1993 Aug;93(2):189–194. doi: 10.1111/j.1365-2249.1993.tb07964.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Girgis R. E., Basha M. A., Maliarik M., Popovich J., Jr, Iannuzzi M. C. Cytokines in the bronchoalveolar lavage fluid of patients with active pulmonary sarcoidosis. Am J Respir Crit Care Med. 1995 Jul;152(1):71–75. doi: 10.1164/ajrccm.152.1.7599865. [DOI] [PubMed] [Google Scholar]
  15. Hamid Q., Azzawi M., Ying S., Moqbel R., Wardlaw A. J., Corrigan C. J., Bradley B., Durham S. R., Collins J. V., Jeffery P. K. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest. 1991 May;87(5):1541–1546. doi: 10.1172/JCI115166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Havell E. A. Evidence that tumor necrosis factor has an important role in antibacterial resistance. J Immunol. 1989 Nov 1;143(9):2894–2899. [PubMed] [Google Scholar]
  17. Hechtman D. H., Cybulsky M. I., Fuchs H. J., Baker J. B., Gimbrone M. A., Jr Intravascular IL-8. Inhibitor of polymorphonuclear leukocyte accumulation at sites of acute inflammation. J Immunol. 1991 Aug 1;147(3):883–892. [PubMed] [Google Scholar]
  18. Kayes S. G., Oaks J. A. Effect of inoculum size and length of infection on the distribution of Toxocara canis larvae in the mouse. Am J Trop Med Hyg. 1976 Jul;25(4):573–580. doi: 10.4269/ajtmh.1976.25.573. [DOI] [PubMed] [Google Scholar]
  19. Kimata H., Yoshida A., Ishioka C., Lindley I., Mikawa H. Interleukin 8 (IL-8) selectively inhibits immunoglobulin E production induced by IL-4 in human B cells. J Exp Med. 1992 Oct 1;176(4):1227–1231. doi: 10.1084/jem.176.4.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kindler V., Sappino A. P., Grau G. E., Piguet P. F., Vassalli P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell. 1989 Mar 10;56(5):731–740. doi: 10.1016/0092-8674(89)90676-4. [DOI] [PubMed] [Google Scholar]
  21. Kunkel S. L., Strieter R. M., Chensue S. W., Basha M., Standiford T., Ham J., Remick D. G. Tumor necrosis factor-alpha, interleukin-8 and chemotactic cytokines. Prog Clin Biol Res. 1990;349:433–444. [PubMed] [Google Scholar]
  22. Limaye A. P., Abrams J. S., Silver J. E., Ottesen E. A., Nutman T. B. Regulation of parasite-induced eosinophilia: selectively increased interleukin 5 production in helminth-infected patients. J Exp Med. 1990 Jul 1;172(1):399–402. doi: 10.1084/jem.172.1.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lukacs N. W., Strieter R. M., Chensue S. W., Widmer M., Kunkel S. L. TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation. J Immunol. 1995 May 15;154(10):5411–5417. [PubMed] [Google Scholar]
  24. Marini M., Vittori E., Hollemborg J., Mattoli S. Expression of the potent inflammatory cytokines, granulocyte-macrophage-colony-stimulating factor and interleukin-6 and interleukin-8, in bronchial epithelial cells of patients with asthma. J Allergy Clin Immunol. 1992 May;89(5):1001–1009. doi: 10.1016/0091-6749(92)90223-o. [DOI] [PubMed] [Google Scholar]
  25. Moser R., Fehr J., Olgiati L., Bruijnzeel P. L. Migration of primed human eosinophils across cytokine-activated endothelial cell monolayers. Blood. 1992 Jun 1;79(11):2937–2945. [PubMed] [Google Scholar]
  26. Nutman T. B., Ottesen E. A., Cohen S. G. The eosinophil, eosinophilia, and eosinophil-related disorders. IV. Eosinophil related disorders (continued). Allergy Proc. 1989 Jan-Feb;10(1):47–62. doi: 10.2500/108854189778968579. [DOI] [PubMed] [Google Scholar]
  27. Ohkawara Y., Yamauchi K., Tanno Y., Tamura G., Ohtani H., Nagura H., Ohkuda K., Takishima T. Human lung mast cells and pulmonary macrophages produce tumor necrosis factor-alpha in sensitized lung tissue after IgE receptor triggering. Am J Respir Cell Mol Biol. 1992 Oct;7(4):385–392. doi: 10.1165/ajrcmb/7.4.385. [DOI] [PubMed] [Google Scholar]
  28. Parsons J. C., Bowman D. D., Grieve R. B. Tissue localization of excretory-secretory antigens of larval Toxocara canis in acute and chronic murine toxocariasis. Am J Trop Med Hyg. 1986 Sep;35(5):974–981. doi: 10.4269/ajtmh.1986.35.974. [DOI] [PubMed] [Google Scholar]
  29. Sehmi R., Cromwell O., Wardlaw A. J., Moqbel R., Kay A. B. Interleukin-8 is a chemo-attractant for eosinophils purified from subjects with a blood eosinophilia but not from normal healthy subjects. Clin Exp Allergy. 1993 Dec;23(12):1027–1036. doi: 10.1111/j.1365-2222.1993.tb00295.x. [DOI] [PubMed] [Google Scholar]
  30. Sheron N., Williams R. IL-8 as a circulating cytokine: induction by recombinant tumour necrosis factor-alpha. Clin Exp Immunol. 1992 Jul;89(1):100–103. doi: 10.1111/j.1365-2249.1992.tb06885.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Weg V. B., Walsh D. T., Faccioli L. H., Williams T. J., Feldmann M., Nourshargh S. LPS-induced 111In-eosinophil accumulation in guinea-pig skin: evidence for a role for TNF-alpha. Immunology. 1995 Jan;84(1):36–40. [PMC free article] [PubMed] [Google Scholar]
  33. Weller P. F., Goetzl E. J. The human eosinophil: roles in host defense and tissue injury. Am J Pathol. 1980 Sep;100(3):791–820. [PMC free article] [PubMed] [Google Scholar]
  34. Yamaguchi Y., Suda T., Suda J., Eguchi M., Miura Y., Harada N., Tominaga A., Takatsu K. Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors. J Exp Med. 1988 Jan 1;167(1):43–56. doi: 10.1084/jem.167.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yoshimura T., Matsushima K., Oppenheim J. J., Leonard E. J. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1). J Immunol. 1987 Aug 1;139(3):788–793. [PubMed] [Google Scholar]
  36. van Deventer S. J., Büller H. R., ten Cate J. W., Aarden L. A., Hack C. E., Sturk A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood. 1990 Dec 15;76(12):2520–2526. [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES