Skip to main content
PMC home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1996 Oct;5(5):334–340. doi: 10.1155/S0962935196000488

Regulation by anti-inflammatory cytokines (IL-4, IL-10, IL-13, TGFβ)of interleukin-8 production by LPS- and/ or TNFα-activated human polymorphonuclear cells

C Marie 1, C Pitton 1, C Fitting 1, J-M Cavaillon 1,✉
PMCID: PMC2365804  PMID: 18475727

Abstract

The capacity to down-regulate the production of IL-8 by LPS-activated human polymorphonuclear cells (PMN) has been demonstrated for IL-4, IL-10, and TGFβ. We compared their relative capacities and further extended this property to IL-13. We report a great heterogeneity among individuals related to the responsiveness of PMN to the IL-4 and IL-13 inhibitory effects while their response to the IL-10 effect was homogenous. The inhibitory activities were observed at the transcriptional level. IL-8 induction by TNFα was, unlike its induction by LPS, resistant to the inhibitory effects of IL-10, IL-4, IL-13 and TGFβ. Furthermore, IL-10 and IL-4 inhibitory activity were less effective when TNFα was acting synergistically with LPS to induce IL-8 production by PMN. LPS-induced cell-associated IL-8, detected in the PMN cultures, could be marginally inhibited by IL-4 and IL-10. Altogether, our data demonstrate that IL-13 is able to inhibit LPS-induced IL-8 production by human PMN, although IL-10 remains the most active anti-inflammatory cytokine. Despite the capacity of IL-4, IL-10, and IL-13 to limit the production of TNFα-induced IL-8 in a whole blood assay, none was able to inhibit this production when studying isolated human polymorphonuclear cells.

Full Text

The Full Text of this article is available as a PDF (854.0 KB).

Selected References

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

  1. Bazzoni F., Cassatella M. A., Rossi F., Ceska M., Dewald B., Baggiolini M. Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8. J Exp Med. 1991 Mar 1;173(3):771–774. doi: 10.1084/jem.173.3.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bender J. R., Sadeghi M. M., Watson C., Pfau S., Pardi R. Heterogeneous activation thresholds to cytokines in genetically distinct endothelial cells: evidence for diverse transcriptional responses. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3994–3998. doi: 10.1073/pnas.91.9.3994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bogdan C., Paik J., Vodovotz Y., Nathan C. Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. J Biol Chem. 1992 Nov 15;267(32):23301–23308. [PubMed] [Google Scholar]
  4. Broaddus V. C., Boylan A. M., Hoeffel J. M., Kim K. J., Sadick M., Chuntharapai A., Hébert C. A. Neutralization of IL-8 inhibits neutrophil influx in a rabbit model of endotoxin-induced pleurisy. J Immunol. 1994 Mar 15;152(6):2960–2967. [PubMed] [Google Scholar]
  5. Cassatella M. A., Meda L., Bonora S., Ceska M., Constantin G. Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. J Exp Med. 1993 Dec 1;178(6):2207–2211. doi: 10.1084/jem.178.6.2207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chollet-Martin S., Montravers P., Gibert C., Elbim C., Desmonts J. M., Fagon J. Y., Gougerot-Pocidalo M. A. High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome. Infect Immun. 1993 Nov;61(11):4553–4559. doi: 10.1128/iai.61.11.4553-4559.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Colditz I., Zwahlen R., Dewald B., Baggiolini M. In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am J Pathol. 1989 Apr;134(4):755–760. [PMC free article] [PubMed] [Google Scholar]
  9. Collins P. D., Jose P. J., Williams T. J. The sequential generation of neutrophil chemoattractant proteins in acute inflammation in the rabbit in vivo. Relationship between C5a and proteins with the characteristics of IL-8/neutrophil-activating protein 1. J Immunol. 1991 Jan 15;146(2):677–684. [PubMed] [Google Scholar]
  10. De Beaux A. C., Maingay J. P., Ross J. A., Fearon K. C., Carter D. C. Interleukin-4 and interleukin-10 increase endotoxin-stimulated human umbilical vein endothelial cell interleukin-8 release. J Interferon Cytokine Res. 1995 May;15(5):441–445. doi: 10.1089/jir.1995.15.441. [DOI] [PubMed] [Google Scholar]
  11. Donnelly S. C., Strieter R. M., Kunkel S. L., Walz A., Robertson C. R., Carter D. C., Grant I. S., Pollok A. J., Haslett C. Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet. 1993 Mar 13;341(8846):643–647. doi: 10.1016/0140-6736(93)90416-e. [DOI] [PubMed] [Google Scholar]
  12. Foster S. J., Aked D. M., Schröder J. M., Christophers E. Acute inflammatory effects of a monocyte-derived neutrophil-activating peptide in rabbit skin. Immunology. 1989 Jun;67(2):181–183. [PMC free article] [PubMed] [Google Scholar]
  13. Friedland J. S., Suputtamongkol Y., Remick D. G., Chaowagul W., Strieter R. M., Kunkel S. L., White N. J., Griffin G. E. Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma and of leukocyte interleukin-8 mRNA levels during septicemic and localized Pseudomonas pseudomallei infection. Infect Immun. 1992 Jun;60(6):2402–2408. doi: 10.1128/iai.60.6.2402-2408.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fujishima S., Hoffman A. R., Vu T., Kim K. J., Zheng H., Daniel D., Kim Y., Wallace E. F., Larrick J. W., Raffin T. A. Regulation of neutrophil interleukin 8 gene expression and protein secretion by LPS, TNF-alpha, and IL-1 beta. J Cell Physiol. 1993 Mar;154(3):478–485. doi: 10.1002/jcp.1041540305. [DOI] [PubMed] [Google Scholar]
  15. Girard D., Paquin R., Naccache P. H., Beaulieu A. D. Effects of interleukin-13 on human neutrophil functions. J Leukoc Biol. 1996 Mar;59(3):412–419. doi: 10.1002/jlb.59.3.412. [DOI] [PubMed] [Google Scholar]
  16. Hack C. E., Hart M., van Schijndel R. J., Eerenberg A. J., Nuijens J. H., Thijs L. G., Aarden L. A. Interleukin-8 in sepsis: relation to shock and inflammatory mediators. Infect Immun. 1992 Jul;60(7):2835–2842. doi: 10.1128/iai.60.7.2835-2842.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hewett J. A., Schultze A. E., VanCise S., Roth R. A. Neutrophil depletion protects against liver injury from bacterial endotoxin. Lab Invest. 1992 Mar;66(3):347–361. [PubMed] [Google Scholar]
  18. Horgan M. J., Palace G. P., Everitt J. E., Malik A. B. TNF-alpha release in endotoxemia contributes to neutrophil-dependent pulmonary edema. Am J Physiol. 1993 Apr;264(4 Pt 2):H1161–H1165. doi: 10.1152/ajpheart.1993.264.4.H1161. [DOI] [PubMed] [Google Scholar]
  19. Izzo R. S., Witkon K., Chen A. I., Hadjiyane C., Weinstein M. I., Pellecchia C. Interleukin-8 and neutrophil markers in colonic mucosa from patients with ulcerative colitis. Am J Gastroenterol. 1992 Oct;87(10):1447–1452. [PubMed] [Google Scholar]
  20. Kasama T., Strieter R. M., Lukacs N. W., Burdick M. D., Kunkel S. L. Regulation of neutrophil-derived chemokine expression by IL-10. J Immunol. 1994 Apr 1;152(7):3559–3569. [PubMed] [Google Scholar]
  21. Kuhns D. B., Gallin J. I. Increased cell-associated IL-8 in human exudative and A23187-treated peripheral blood neutrophils. J Immunol. 1995 Jun 15;154(12):6556–6562. [PubMed] [Google Scholar]
  22. Mallick A. A., Ishizaka A., Stephens K. E., Hatherill J. R., Tazelaar H. D., Raffin T. A. Multiple organ damage caused by tumor necrosis factor and prevented by prior neutrophil depletion. Chest. 1989 May;95(5):1114–1120. doi: 10.1378/chest.95.5.1114. [DOI] [PubMed] [Google Scholar]
  23. Marie C., Pitton C., Fitting C., Cavaillon J. M. IL-10 and IL-4 synergize with TNF-alpha to induce IL-1ra production by human neutrophils. Cytokine. 1996 Feb;8(2):147–151. doi: 10.1006/cyto.1996.0021. [DOI] [PubMed] [Google Scholar]
  24. Marty C., Misset B., Tamion F., Fitting C., Carlet J., Cavaillon J. M. Circulating interleukin-8 concentrations in patients with multiple organ failure of septic and nonseptic origin. Crit Care Med. 1994 Apr;22(4):673–679. doi: 10.1097/00003246-199404000-00025. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Miller E. J., Cohen A. B., Nagao S., Griffith D., Maunder R. J., Martin T. R., Weiner-Kronish J. P., Sticherling M., Christophers E., Matthay M. A. Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am Rev Respir Dis. 1992 Aug;146(2):427–432. doi: 10.1164/ajrccm/146.2.427. [DOI] [PubMed] [Google Scholar]
  27. Mulligan M. S., Jones M. L., Bolanowski M. A., Baganoff M. P., Deppeler C. L., Meyers D. M., Ryan U. S., Ward P. A. Inhibition of lung inflammatory reactions in rats by an anti-human IL-8 antibody. J Immunol. 1993 Jun 15;150(12):5585–5595. [PubMed] [Google Scholar]
  28. Nuijens J. H., Abbink J. J., Wachtfogel Y. T., Colman R. W., Eerenberg A. J., Dors D., Kamp A. J., Strack van Schijndel R. J., Thijs L. G., Hack C. E. Plasma elastase alpha 1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis. J Lab Clin Med. 1992 Feb;119(2):159–168. [PubMed] [Google Scholar]
  29. Remick D. G., DeForge L. E., Sullivan J. F., Showell H. J. Profile of cytokines in synovial fluid specimens from patients with arthritis. Interleukin 8 (IL-8) and IL-6 correlate with inflammatory arthritides. Immunol Invest. 1992 Jul;21(4):321–327. doi: 10.3109/08820139209069371. [DOI] [PubMed] [Google Scholar]
  30. Romagnani S. Induction of TH1 and TH2 responses: a key role for the 'natural' immune response? Immunol Today. 1992 Oct;13(10):379–381. doi: 10.1016/0167-5699(92)90083-J. [DOI] [PubMed] [Google Scholar]
  31. Samanta A. K., Oppenheim J. J., Matsushima K. Interleukin 8 (monocyte-derived neutrophil chemotactic factor) dynamically regulates its own receptor expression on human neutrophils. J Biol Chem. 1990 Jan 5;265(1):183–189. [PubMed] [Google Scholar]
  32. Sato T., Shinzawa H., Abe Y., Takahashi T., Arai S., Sendo F. Inhibition of Corynebacterium parvum-primed and lipopolysaccharide-induced hepatic necrosis in rats by selective depletion of neutrophils using a monoclonal antibody. J Leukoc Biol. 1993 Feb;53(2):144–150. doi: 10.1002/jlb.53.2.144. [DOI] [PubMed] [Google Scholar]
  33. Sekido N., Mukaida N., Harada A., Nakanishi I., Watanabe Y., Matsushima K. Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature. 1993 Oct 14;365(6447):654–657. doi: 10.1038/365654a0. [DOI] [PubMed] [Google Scholar]
  34. Strieter R. M., Kasahara K., Allen R. M., Standiford T. J., Rolfe M. W., Becker F. S., Chensue S. W., Kunkel S. L. Cytokine-induced neutrophil-derived interleukin-8. Am J Pathol. 1992 Aug;141(2):397–407. [PMC free article] [PubMed] [Google Scholar]
  35. Wang P., Wu P., Anthes J. C., Siegel M. I., Egan R. W., Billah M. M. Interleukin-10 inhibits interleukin-8 production in human neutrophils. Blood. 1994 May 1;83(9):2678–2683. [PubMed] [Google Scholar]
  36. Wei S., Liu J. H., Blanchard D. K., Djeu J. Y. Induction of IL-8 gene expression in human polymorphonuclear neutrophils by recombinant IL-2. J Immunol. 1994 Apr 1;152(7):3630–3636. [PubMed] [Google Scholar]
  37. Weiss L., Haeffner-Cavaillon N., Laude M., Cavaillon J. M., Kazatchkine M. D. Human T cells and interleukin 4 inhibit the release of interleukin 1 induced by lipopolysaccharide in serum-free cultures of autologous monocytes. Eur J Immunol. 1989 Jul;19(7):1347–1350. doi: 10.1002/eji.1830190731. [DOI] [PubMed] [Google Scholar]
  38. Wertheim W. A., Kunkel S. L., Standiford T. J., Burdick M. D., Becker F. S., Wilke C. A., Gilbert A. R., Strieter R. M. Regulation of neutrophil-derived IL-8: the role of prostaglandin E2, dexamethasone, and IL-4. J Immunol. 1993 Aug 15;151(4):2166–2175. [PubMed] [Google Scholar]
  39. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. de Waal Malefyt R., Figdor C. G., Huijbens R., Mohan-Peterson S., Bennett B., Culpepper J., Dang W., Zurawski G., de Vries J. E. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J Immunol. 1993 Dec 1;151(11):6370–6381. [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES