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. 1997 Feb;65(2):395–404. doi: 10.1128/iai.65.2.395-404.1997

Salmonella typhi stimulation of human intestinal epithelial cells induces secretion of epithelial cell-derived interleukin-6.

D L Weinstein 1, B L O'Neill 1, E S Metcalf 1
PMCID: PMC174608  PMID: 9009288

Abstract

Interleukin 6 (IL-6) is a multifunctional cytokine that has been shown to be associated with both systemic and tissue-specific responses within the host. Moreover, IL-6 is produced by both lymphoid and nonlymphoid cells and has been identified as a growth-inducing, growth-inhibiting, and differentiation-inducing factor for these cells. Recent studies of uropathogenic and upper respiratory pathogens have suggested that epithelial cell-derived IL-6 plays a role in mucosal host-parasite interactions. Since many mucosal enteric pathogens enter the host through the epithelial cells of the distal small intestine, a role for intestinal epithelial cell-derived IL-6 in the initial interaction between bacteria and host might also be predicted. However, no studies to date have determined whether the interaction of any bacteria with the epithelial cells that line the small intestine of the host can induce IL-6. To address this issue, we have established an in vitro model to evaluate the capacity of the gram-negative bacterium Salmonella typhi to induce IL-6 in the small intestine epithelial cell line Int407 and in other intestinal epithelial cell lines. The results demonstrate that both wild-type and live, attenuated S. typhi vaccine strains induce small and large intestine epithelial cells to secrete IL-6, and kinetic analysis suggests that IL-6 may be one of the earliest responses following adherence and invasion of enteric organisms. Thus, these studies suggest a physiologic role for epithelial cell-derived IL-6 in the initial interactions between host and bacterium in the small intestine.

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Selected References

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  1. Aderka D., Le J. M., Vilcek J. IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. J Immunol. 1989 Dec 1;143(11):3517–3523. [PubMed] [Google Scholar]
  2. Agace W. W., Hedges S. R., Ceska M., Svanborg C. Interleukin-8 and the neutrophil response to mucosal gram-negative infection. J Clin Invest. 1993 Aug;92(2):780–785. doi: 10.1172/JCI116650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Agace W., Hedges S., Andersson U., Andersson J., Ceska M., Svanborg C. Selective cytokine production by epithelial cells following exposure to Escherichia coli. Infect Immun. 1993 Feb;61(2):602–609. doi: 10.1128/iai.61.2.602-609.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Akira S., Kishimoto T. IL-6 and NF-IL6 in acute-phase response and viral infection. Immunol Rev. 1992 Jun;127:25–50. doi: 10.1111/j.1600-065x.1992.tb01407.x. [DOI] [PubMed] [Google Scholar]
  5. Arnold R., Scheffer J., König B., König W. Effects of Listeria monocytogenes and Yersinia enterocolitica on cytokine gene expression and release from human polymorphonuclear granulocytes and epithelial (HEp-2) cells. Infect Immun. 1993 Jun;61(6):2545–2552. doi: 10.1128/iai.61.6.2545-2552.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ballester O. F., Moscinski L. C., Lyman G. H., Chaney J. V., Saba H. I., Spiers A. S., Klein C. High levels of interleukin-6 are associated with low tumor burden and low growth fraction in multiple myeloma. Blood. 1994 Apr 1;83(7):1903–1908. [PubMed] [Google Scholar]
  7. Barton B. E., Jackson J. V. Protective role of interleukin 6 in the lipopolysaccharide-galactosamine septic shock model. Infect Immun. 1993 Apr;61(4):1496–1499. doi: 10.1128/iai.61.4.1496-1499.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bataille R., Jourdan M., Zhang X. G., Klein B. Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias. J Clin Invest. 1989 Dec;84(6):2008–2011. doi: 10.1172/JCI114392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Baumann H., Gauldie J. Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulating factors and other mediators of inflammation. Mol Biol Med. 1990 Apr;7(2):147–159. [PubMed] [Google Scholar]
  10. Beagley K. W., Eldridge J. H., Aicher W. K., Mestecky J., Di Fabio S., Kiyono H., McGhee J. R. Peyer's patch B cells with memory cell characteristics undergo terminal differentiation within 24 hours in response to interleukin-6. Cytokine. 1991 Mar;3(2):107–116. doi: 10.1016/1043-4666(91)90030-h. [DOI] [PubMed] [Google Scholar]
  11. Beagley K. W., Eldridge J. H., Lee F., Kiyono H., Everson M. P., Koopman W. J., Hirano T., Kishimoto T., McGhee J. R. Interleukins and IgA synthesis. Human and murine interleukin 6 induce high rate IgA secretion in IgA-committed B cells. J Exp Med. 1989 Jun 1;169(6):2133–2148. doi: 10.1084/jem.169.6.2133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Crabtree J. E., Wyatt J. I., Trejdosiewicz L. K., Peichl P., Nichols P. H., Ramsay N., Primrose J. N., Lindley I. J. Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic gastroduodenal mucosa. J Clin Pathol. 1994 Jan;47(1):61–66. doi: 10.1136/jcp.47.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Croft M., Swain S. L. B cell response to T helper cell subsets. II. Both the stage of T cell differentiation and the cytokines secreted determine the extent and nature of helper activity. J Immunol. 1991 Dec 1;147(11):3679–3689. [PubMed] [Google Scholar]
  14. Dalrymple S. A., Lucian L. A., Slattery R., McNeil T., Aud D. M., Fuchino S., Lee F., Murray R. Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia. Infect Immun. 1995 Jun;63(6):2262–2268. doi: 10.1128/iai.63.6.2262-2268.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. DiMango E., Zar H. J., Bryan R., Prince A. Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8. J Clin Invest. 1995 Nov;96(5):2204–2210. doi: 10.1172/JCI118275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Eckmann L., Jung H. C., Schürer-Maly C., Panja A., Morzycka-Wroblewska E., Kagnoff M. F. Differential cytokine expression by human intestinal epithelial cell lines: regulated expression of interleukin 8. Gastroenterology. 1993 Dec;105(6):1689–1697. doi: 10.1016/0016-5085(93)91064-o. [DOI] [PubMed] [Google Scholar]
  17. Eckmann L., Kagnoff M. F., Fierer J. Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry. Infect Immun. 1993 Nov;61(11):4569–4574. doi: 10.1128/iai.61.11.4569-4574.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Elsinghorst E. A., Baron L. S., Kopecko D. J. Penetration of human intestinal epithelial cells by Salmonella: molecular cloning and expression of Salmonella typhi invasion determinants in Escherichia coli. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5173–5177. doi: 10.1073/pnas.86.13.5173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fattori E., Cappelletti M., Costa P., Sellitto C., Cantoni L., Carelli M., Faggioni R., Fantuzzi G., Ghezzi P., Poli V. Defective inflammatory response in interleukin 6-deficient mice. J Exp Med. 1994 Oct 1;180(4):1243–1250. doi: 10.1084/jem.180.4.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fogh J., Wright W. C., Loveless J. D. Absence of HeLa cell contamination in 169 cell lines derived from human tumors. J Natl Cancer Inst. 1977 Feb;58(2):209–214. doi: 10.1093/jnci/58.2.209. [DOI] [PubMed] [Google Scholar]
  21. Galán J. E., Curtiss R., 3rd Distribution of the invA, -B, -C, and -D genes of Salmonella typhimurium among other Salmonella serovars: invA mutants of Salmonella typhi are deficient for entry into mammalian cells. Infect Immun. 1991 Sep;59(9):2901–2908. doi: 10.1128/iai.59.9.2901-2908.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. HENLE G., DEINHARDT F. The establishment of strains of human cells in tissue culture. J Immunol. 1957 Jul;79(1):54–59. [PubMed] [Google Scholar]
  23. Hedges S., Stenqvist K., Lidin-Janson G., Martinell J., Sandberg T., Svanborg C. Comparison of urine and serum concentrations of interleukin-6 in women with acute pyelonephritis or asymptomatic bacteriuria. J Infect Dis. 1992 Sep;166(3):653–656. doi: 10.1093/infdis/166.3.653. [DOI] [PubMed] [Google Scholar]
  24. Hedges S., Svensson M., Svanborg C. Interleukin-6 response of epithelial cell lines to bacterial stimulation in vitro. Infect Immun. 1992 Apr;60(4):1295–1301. doi: 10.1128/iai.60.4.1295-1301.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Heinrich P. C., Castell J. V., Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990 Feb 1;265(3):621–636. doi: 10.1042/bj2650621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Heremans H., Dillen C., Put W., Van Damme J., Billiau A. Protective effect of anti-interleukin (IL)-6 antibody against endotoxin, associated with paradoxically increased IL-6 levels. Eur J Immunol. 1992 Sep;22(9):2395–2401. doi: 10.1002/eji.1830220932. [DOI] [PubMed] [Google Scholar]
  27. Hilbert D. M., Kopf M., Mock B. A., Köhler G., Rudikoff S. Interleukin 6 is essential for in vivo development of B lineage neoplasms. J Exp Med. 1995 Jul 1;182(1):243–248. doi: 10.1084/jem.182.1.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hirano T., Akira S., Taga T., Kishimoto T. Biological and clinical aspects of interleukin 6. Immunol Today. 1990 Dec;11(12):443–449. doi: 10.1016/0167-5699(90)90173-7. [DOI] [PubMed] [Google Scholar]
  29. Hirano T., Taga T., Nakano N., Yasukawa K., Kashiwamura S., Shimizu K., Nakajima K., Pyun K. H., Kishimoto T. Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci U S A. 1985 Aug;82(16):5490–5494. doi: 10.1073/pnas.82.16.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Holsti M. A., Raulet D. H. IL-6 and IL-1 synergize to stimulate IL-2 production and proliferation of peripheral T cells. J Immunol. 1989 Oct 15;143(8):2514–2519. [PubMed] [Google Scholar]
  31. Hone D. M., Tacket C. O., Harris A. M., Kay B., Losonsky G., Levine M. M. Evaluation in volunteers of a candidate live oral attenuated Salmonella typhi vector vaccine. J Clin Invest. 1992 Aug;90(2):412–420. doi: 10.1172/JCI115876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Houssiau F. A., Coulie P. G., Van Snick J. Distinct roles of IL-1 and IL-6 in human T cell activation. J Immunol. 1989 Oct 15;143(8):2520–2524. [PubMed] [Google Scholar]
  33. Huang J., O'Toole P. W., Doig P., Trust T. J. Stimulation of interleukin-8 production in epithelial cell lines by Helicobacter pylori. Infect Immun. 1995 May;63(5):1732–1738. doi: 10.1128/iai.63.5.1732-1738.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ikebuchi K., Wong G. G., Clark S. C., Ihle J. N., Hirai Y., Ogawa M. Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9035–9039. doi: 10.1073/pnas.84.24.9035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Jones S. C., Trejdosiewicz L. K., Banks R. E., Howdle P. D., Axon A. T., Dixon M. F., Whicher J. T. Expression of interleukin-6 by intestinal enterocytes. J Clin Pathol. 1993 Dec;46(12):1097–1100. doi: 10.1136/jcp.46.12.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Jordan M., Otterness I. G., Ng R., Gessner A., Röllinghoff M., Beuscher H. U. Neutralization of endogenous IL-6 suppresses induction of IL-1 receptor antagonist. J Immunol. 1995 Apr 15;154(8):4081–4090. [PubMed] [Google Scholar]
  37. Jung H. C., Eckmann L., Yang S. K., Panja A., Fierer J., Morzycka-Wroblewska E., Kagnoff M. F. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest. 1995 Jan;95(1):55–65. doi: 10.1172/JCI117676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Keuter M., Dharmana E., Gasem M. H., van der Ven-Jongekrijg J., Djokomoeljanto R., Dolmans W. M., Demacker P., Sauerwein R., Gallati H., van der Meer J. W. Patterns of proinflammatory cytokines and inhibitors during typhoid fever. J Infect Dis. 1994 Jun;169(6):1306–1311. doi: 10.1093/infdis/169.6.1306. [DOI] [PubMed] [Google Scholar]
  39. Kihlström E., Nilsson L. Endocytosis of Salmonella typhimurium 395 MS and MR10 by HeLa cells. Acta Pathol Microbiol Scand B. 1977 Oct;85B(5):322–328. doi: 10.1111/j.1699-0463.1977.tb01982.x. [DOI] [PubMed] [Google Scholar]
  40. Kishimoto T., Akira S., Taga T. Interleukin-6 and its receptor: a paradigm for cytokines. Science. 1992 Oct 23;258(5082):593–597. doi: 10.1126/science.1411569. [DOI] [PubMed] [Google Scholar]
  41. Kishimoto T., Taga T., Akira S. Cytokine signal transduction. Cell. 1994 Jan 28;76(2):253–262. doi: 10.1016/0092-8674(94)90333-6. [DOI] [PubMed] [Google Scholar]
  42. Klimpel G. R., Asuncion M., Haithcoat J., Niesel D. W. Cholera toxin and Salmonella typhimurium induce different cytokine profiles in the gastrointestinal tract. Infect Immun. 1995 Mar;63(3):1134–1137. doi: 10.1128/iai.63.3.1134-1137.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Kopf M., Baumann H., Freer G., Freudenberg M., Lamers M., Kishimoto T., Zinkernagel R., Bluethmann H., Köhler G. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature. 1994 Mar 24;368(6469):339–342. doi: 10.1038/368339a0. [DOI] [PubMed] [Google Scholar]
  44. Lee W. T., Vitetta E. S. Virgin T cells do not provide help for antigen-specific B cells in the absence of IL-4, IL-5, and IL-6. Int Immunol. 1991 Sep;3(9):907–916. doi: 10.1093/intimm/3.9.907. [DOI] [PubMed] [Google Scholar]
  45. Liu Z., Cheers C. The cellular source of interleukin-6 during Listeria infection. Infect Immun. 1993 Jun;61(6):2626–2631. doi: 10.1128/iai.61.6.2626-2631.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Liu Z., Simpson R. J., Cheers C. Recombinant interleukin-6 protects mice against experimental bacterial infection. Infect Immun. 1992 Oct;60(10):4402–4406. doi: 10.1128/iai.60.10.4402-4406.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Manthey C. L., Perera P. Y., Salkowski C. A., Vogel S. N. Taxol provides a second signal for murine macrophage tumoricidal activity. J Immunol. 1994 Jan 15;152(2):825–831. [PubMed] [Google Scholar]
  48. McCormick B. A., Colgan S. P., Delp-Archer C., Miller S. I., Madara J. L. Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils. J Cell Biol. 1993 Nov;123(4):895–907. doi: 10.1083/jcb.123.4.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. McGee D. W., Beagley K. W., Aicher W. K., McGhee J. R. Transforming growth factor-beta and IL-1 beta act in synergy to enhance IL-6 secretion by the intestinal epithelial cell line, IEC-6. J Immunol. 1993 Jul 15;151(2):970–978. [PubMed] [Google Scholar]
  50. McGee D. W., Beagley K. W., Aicher W. K., McGhee J. R. Transforming growth factor-beta enhances interleukin-6 secretion by intestinal epithelial cells. Immunology. 1992 Sep;77(1):7–12. [PMC free article] [PubMed] [Google Scholar]
  51. McGee D. W., Elson C. O., McGhee J. R. Enhancing effect of cholera toxin on interleukin-6 secretion by IEC-6 intestinal epithelial cells: mode of action and augmenting effect of inflammatory cytokines. Infect Immun. 1993 Nov;61(11):4637–4644. doi: 10.1128/iai.61.11.4637-4644.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. McGhee J. R., Mestecky J., Elson C. O., Kiyono H. Regulation of IgA synthesis and immune response by T cells and interleukins. J Clin Immunol. 1989 May;9(3):175–199. doi: 10.1007/BF00916814. [DOI] [PubMed] [Google Scholar]
  53. Mills S. D., Finlay B. B. Comparison of Salmonella typhi and Salmonella typhimurium invasion, intracellular growth and localization in cultured human epithelial cells. Microb Pathog. 1994 Dec;17(6):409–423. doi: 10.1006/mpat.1994.1086. [DOI] [PubMed] [Google Scholar]
  54. Nachbaur D. M., Herold M., Maneschg A., Huber H. Serum levels of interleukin-6 in multiple myeloma and other hematological disorders: correlation with disease activity and other prognostic parameters. Ann Hematol. 1991 Feb-Mar;62(2-3):54–58. doi: 10.1007/BF01714900. [DOI] [PubMed] [Google Scholar]
  55. Natelson B. H., Zhou X., Ottenweller J. E., Bergen M. T., Sisto S. A., Drastal S., Tapp W. N., Gause W. L. Effect of acute exhausting exercise on cytokine gene expression in men. Int J Sports Med. 1996 May;17(4):299–302. doi: 10.1055/s-2007-972850. [DOI] [PubMed] [Google Scholar]
  56. Oelschlaeger T. A., Barrett T. J., Kopecko D. J. Some structures and processes of human epithelial cells involved in uptake of enterohemorrhagic Escherichia coli O157:H7 strains. Infect Immun. 1994 Nov;62(11):5142–5150. doi: 10.1128/iai.62.11.5142-5150.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Oldenburg H. S., Rogy M. A., Lazarus D. D., Van Zee K. J., Keeler B. P., Chizzonite R. A., Lowry S. F., Moldawer L. L. Cachexia and the acute-phase protein response in inflammation are regulated by interleukin-6. Eur J Immunol. 1993 Aug;23(8):1889–1894. doi: 10.1002/eji.1830230824. [DOI] [PubMed] [Google Scholar]
  58. Quaroni A., Wands J., Trelstad R. L., Isselbacher K. J. Epithelioid cell cultures from rat small intestine. Characterization by morphologic and immunologic criteria. J Cell Biol. 1979 Feb;80(2):248–265. doi: 10.1083/jcb.80.2.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Ramsay A. J., Husband A. J., Ramshaw I. A., Bao S., Matthaei K. I., Koehler G., Kopf M. The role of interleukin-6 in mucosal IgA antibody responses in vivo. Science. 1994 Apr 22;264(5158):561–563. doi: 10.1126/science.8160012. [DOI] [PubMed] [Google Scholar]
  60. Raqib R., Lindberg A. A., Wretlind B., Bardhan P. K., Andersson U., Andersson J. Persistence of local cytokine production in shigellosis in acute and convalescent stages. Infect Immun. 1995 Jan;63(1):289–296. doi: 10.1128/iai.63.1.289-296.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Raqib R., Wretlind B., Andersson J., Lindberg A. A. Cytokine secretion in acute shigellosis is correlated to disease activity and directed more to stool than to plasma. J Infect Dis. 1995 Feb;171(2):376–384. doi: 10.1093/infdis/171.2.376. [DOI] [PubMed] [Google Scholar]
  62. Rogers L. A., Zlotnik A., Lee F., Shortman K. Lymphokine requirements for the development of specific cytotoxic T cells from single precursors. Eur J Immunol. 1991 Apr;21(4):1069–1072. doi: 10.1002/eji.1830210432. [DOI] [PubMed] [Google Scholar]
  63. Schindler R., Mancilla J., Endres S., Ghorbani R., Clark S. C., Dinarello C. A. Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood. 1990 Jan 1;75(1):40–47. [PubMed] [Google Scholar]
  64. Sharma S. A., Tummuru M. K., Miller G. G., Blaser M. J. Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect Immun. 1995 May;63(5):1681–1687. doi: 10.1128/iai.63.5.1681-1687.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Shirota K., LeDuy L., Yuan S. Y., Jothy S. Interleukin-6 and its receptor are expressed in human intestinal epithelial cells. Virchows Arch B Cell Pathol Incl Mol Pathol. 1990;58(4):303–308. doi: 10.1007/BF02890085. [DOI] [PubMed] [Google Scholar]
  66. Sztein M. B., Wasserman S. S., Tacket C. O., Edelman R., Hone D., Lindberg A. A., Levine M. M. Cytokine production patterns and lymphoproliferative responses in volunteers orally immunized with attenuated vaccine strains of Salmonella typhi. J Infect Dis. 1994 Dec;170(6):1508–1517. doi: 10.1093/infdis/170.6.1508. [DOI] [PubMed] [Google Scholar]
  67. Tacket C. O., Hone D. M., Curtiss R., 3rd, Kelly S. M., Losonsky G., Guers L., Harris A. M., Edelman R., Levine M. M. Comparison of the safety and immunogenicity of delta aroC delta aroD and delta cya delta crp Salmonella typhi strains in adult volunteers. Infect Immun. 1992 Feb;60(2):536–541. doi: 10.1128/iai.60.2.536-541.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Tacket C. O., Hone D. M., Losonsky G. A., Guers L., Edelman R., Levine M. M. Clinical acceptability and immunogenicity of CVD 908 Salmonella typhi vaccine strain. Vaccine. 1992;10(7):443–446. doi: 10.1016/0264-410x(92)90392-w. [DOI] [PubMed] [Google Scholar]
  69. Tartera C., Metcalf E. S. Osmolarity and growth phase overlap in regulation of Salmonella typhi adherence to and invasion of human intestinal cells. Infect Immun. 1993 Jul;61(7):3084–3089. doi: 10.1128/iai.61.7.3084-3089.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Tilg H., Trehu E., Atkins M. B., Dinarello C. A., Mier J. W. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood. 1994 Jan 1;83(1):113–118. [PubMed] [Google Scholar]
  71. Ulich T. R., Yin S., Guo K., Yi E. S., Remick D., del Castillo J. Intratracheal injection of endotoxin and cytokines. II. Interleukin-6 and transforming growth factor beta inhibit acute inflammation. Am J Pathol. 1991 May;138(5):1097–1101. [PMC free article] [PubMed] [Google Scholar]
  72. Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–278. doi: 10.1146/annurev.iy.08.040190.001345. [DOI] [PubMed] [Google Scholar]
  73. de Man P., van Kooten C., Aarden L., Engberg I., Linder H., Svanborg Edén C. Interleukin-6 induced at mucosal surfaces by gram-negative bacterial infection. Infect Immun. 1989 Nov;57(11):3383–3388. doi: 10.1128/iai.57.11.3383-3388.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. van der Poll T., Levi M., Hack C. E., ten Cate H., van Deventer S. J., Eerenberg A. J., de Groot E. R., Jansen J., Gallati H., Büller H. R. Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med. 1994 Apr 1;179(4):1253–1259. doi: 10.1084/jem.179.4.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]

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