Skip to main content
Gut logoLink to Gut
. 1992 Jul;33(7):897–901. doi: 10.1136/gut.33.7.897

Interferon-alpha (IFN-alpha) production by human intestinal mononuclear cells. Response to virus in control subjects and in Crohn's disease.

M R Capobianchi 1, S Fais 1, F Mercuri 1, M Boirivant 1, F Dianzani 1, F Pallone 1
PMCID: PMC1379401  PMID: 1644329

Abstract

The virus induced production of interferon alpha by human intestinal lamina propria mononuclear cells was investigated. Intestinal and autologous peripheral cells from control subjects and patients with Crohn's disease were cultured in vitro with and without stimulation with the Newcastle disease virus. Interferon alpha was measured and characterised in the culture supernatants after 12 hours and the kinetics of production was evaluated over the following four days of culture. No detectable interferon alpha was found in cultures of unstimulated intestinal and autologous peripheral mononuclear cells from controls and Crohn's disease whereas interferon alpha was released in all cultures stimulated with the virus. In all 12 hours experiments in both groups, virus stimulated intestinal mononuclear cells yielded significantly less interferon alpha than the autologous peripheral cells. The kinetics experiments showed that control intestinal mononuclear cells appeared to be poorly responsive to virus stimulation showing a release of interferon alpha significantly lower than that of the autologous peripheral cells. The interferon alpha release at day 4 by control cells (either intestinal or peripheral) did not differ from that measured after the first 12 hours. In contrast, the interferon alpha produced by Crohn's disease cells progressively increased during the culture period and the amount of interferon alpha measured at day 4 was significantly higher than that released at 12 hours. These data suggest that normal human intestinal mononuclear cells are down regulated in their capability of producing interferon alpha and that in Crohn's disease their activation for this function is enhanced. These data also suggest that in Crohn's disease intestinal mononuclear cells exhibit a transient hyporesponsiveness to in vitro stimulation possibly related to massive in vivo exposure to interferon alpha inducers.

Full text

PDF
898

Selected References

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

  1. Bocci V. Roles of interferon produced in physiological conditions. A speculative review. Immunology. 1988 May;64(1):1–9. [PMC free article] [PubMed] [Google Scholar]
  2. Boirivant M., Quintieri F., Pugliese O., Famularo G., Fais S., Pallone F. A limiting-dilution analysis of activated circulating B cells in Crohn's disease. J Clin Immunol. 1990 Mar;10(2):128–134. doi: 10.1007/BF00918195. [DOI] [PubMed] [Google Scholar]
  3. Brehm G., Kirchner H. Analysis of the interferons induced in mice in vivo and in macrophages in vitro by Newcastle disease virus and by polyinosinic-polycytidylic acid. J Interferon Res. 1986 Feb;6(1):21–28. doi: 10.1089/jir.1986.6.21. [DOI] [PubMed] [Google Scholar]
  4. Bull D. M., Bookman M. A. Isolation and functional characterization of human intestinal mucosal lymphoid cells. J Clin Invest. 1977 May;59(5):966–974. doi: 10.1172/JCI108719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Capobianchi M. R., De Marco F., Di Marco P., Dianzani F. Acid-labile human interferon alpha production by peripheral blood mononuclear cells stimulated by HIV-infected cells. Arch Virol. 1988;99(1-2):9–19. doi: 10.1007/BF01311019. [DOI] [PubMed] [Google Scholar]
  6. Capobianchi M. R., Facchini J., Di Marco P., Antonelli G., Dianzani F. Induction of alpha interferon by membrane interaction between viral surface and peripheral blood mononuclear cells. Proc Soc Exp Biol Med. 1985 Apr;178(4):551–556. doi: 10.3181/00379727-178-42041. [DOI] [PubMed] [Google Scholar]
  7. Capobianchi M. R., Lorino G., Lun M. T., Mancini C., Di Marco P., Dianzani F. Membrane interactions involved in the induction of interferon-alpha by Mycoplasma pneumoniae. Antiviral Res. 1987 Oct;8(3):115–124. doi: 10.1016/0166-3542(87)90065-9. [DOI] [PubMed] [Google Scholar]
  8. Capobianchi M. R., Malavasi F., Di Marco P., Dianzani F. Differences in the mechanism of induction of interferon-alpha by herpes simplex virus and herpes simplex virus-infected cells. Arch Virol. 1988;103(3-4):219–229. doi: 10.1007/BF01311094. [DOI] [PubMed] [Google Scholar]
  9. Fais S., Capobianchi M. R., Pallone F., Di Marco P., Boirivant M., Dianzani F., Torsoli A. Spontaneous release of interferon gamma by intestinal lamina propria lymphocytes in Crohn's disease. Kinetics of in vitro response to interferon gamma inducers. Gut. 1991 Apr;32(4):403–407. doi: 10.1136/gut.32.4.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fais S., Pallone F., Squarcia O., Biancone L., Ricci F., Paoluzi P., Boirivant M. HLA-DR antigens on colonic epithelial cells in inflammatory bowel disease: I. Relation to the state of activation of lamina propria lymphocytes and to the epithelial expression of other surface markers. Clin Exp Immunol. 1987 Jun;68(3):605–612. [PMC free article] [PubMed] [Google Scholar]
  11. Fais S., Pallone F., Squarcia O., Boirivant M., Pozzilli P. T cell early activation antigens expressed by peripheral lymphocytes in Crohn's disease. J Clin Lab Immunol. 1985 Feb;16(2):75–76. [PubMed] [Google Scholar]
  12. Fiocchi C., Hilfiker M. L., Youngman K. R., Doerder N. C., Finke J. H. Interleukin 2 activity of human intestinal mucosa mononuclear cells. Decreased levels in inflammatory bowel disease. Gastroenterology. 1984 Apr;86(4):734–742. [PubMed] [Google Scholar]
  13. Harvey R. F., Bradshaw J. M. A simple index of Crohn's-disease activity. Lancet. 1980 Mar 8;1(8167):514–514. doi: 10.1016/s0140-6736(80)92767-1. [DOI] [PubMed] [Google Scholar]
  14. Hooks J. J., Moutsopoulos H. M., Notkins A. L. Circulating interferon in human autoimmune diseases. Tex Rep Biol Med. 1981;41:164–168. [PubMed] [Google Scholar]
  15. Kirchner H. The interferon system as an integral part of the defense system against infections. Antiviral Res. 1986 Jan;6(1):1–17. doi: 10.1016/0166-3542(86)90035-5. [DOI] [PubMed] [Google Scholar]
  16. Lebon P., Commoy-Chevalier M. J., Robert-Galliot B., Chany C. Different mechanisms for alpha and beta interferon induction. Virology. 1982 Jun;119(2):504–507. doi: 10.1016/0042-6822(82)90109-x. [DOI] [PubMed] [Google Scholar]
  17. MacDonald T. T., Hutchings P., Choy M. Y., Murch S., Cooke A. Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol. 1990 Aug;81(2):301–305. doi: 10.1111/j.1365-2249.1990.tb03334.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mahida Y. R., Patel S., Wu K., Jewell D. P. Interleukin 2 receptor expression by macrophages in inflammatory bowel disease. Clin Exp Immunol. 1988 Dec;74(3):382–386. [PMC free article] [PubMed] [Google Scholar]
  19. Mahida Y. R., Wu K. C., Jewell D. P. Respiratory burst activity of intestinal macrophages in normal and inflammatory bowel disease. Gut. 1989 Oct;30(10):1362–1370. doi: 10.1136/gut.30.10.1362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mahida Y. R., Wu K., Jewell D. P. Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis of Crohn's disease. Gut. 1989 Jun;30(6):835–838. doi: 10.1136/gut.30.6.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pallone F., Fais S., Squarcia O., Biancone L., Pozzilli P., Boirivant M. Activation of peripheral blood and intestinal lamina propria lymphocytes in Crohn's disease. In vivo state of activation and in vitro response to stimulation as defined by the expression of early activation antigens. Gut. 1987 Jun;28(6):745–753. doi: 10.1136/gut.28.6.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pallone F., Matricardi P. M., Squarcia O., Fais S., Le Moli S., Boirivant M., Paoluzi P., D'Amelio R. Raised serum levels of IgM-rheumatoid factor and anti-F(ab')2 autoantibodies in patients with active inflammatory bowel disease. J Clin Lab Immunol. 1986 Apr;19(4):175–180. [PubMed] [Google Scholar]
  23. Raedler A., Fraenkel S., Klose G., Seyfarth K., Thiele H. G. Involvement of the immune system in the pathogenesis of Crohn's disease. Expression of the T9 antigen on peripheral immunocytes correlates with the severity of the disease. Gastroenterology. 1985 Apr;88(4):978–983. doi: 10.1016/s0016-5085(85)80017-2. [DOI] [PubMed] [Google Scholar]
  24. Roberts N. J., Jr, Douglas R. G., Jr, Simons R. M., Diamond M. E. Virus-induced interferon production by human macrophages. J Immunol. 1979 Jul;123(1):365–369. [PubMed] [Google Scholar]
  25. Saksela E., Virtanen I., Hovi T., Secher D. S., Cantell K. Monocyte is the main producer of human leukocyte alpha interferons following Sendai virus induction. Prog Med Virol. 1984;30:78–86. [PubMed] [Google Scholar]
  26. Smith E. M., Johnson H. M., Blalock J. E. Staphylococcus aureus protein A induces the production of interferon-alpha in human lymphocytes and interferon-alpha/beta in mouse spleen cells. J Immunol. 1983 Feb;130(2):773–776. [PubMed] [Google Scholar]
  27. Squarcia O., Fais S., Boirivant M., Di Paolo M. C., Marcheggiano A., Iannoni C., Paoluzi P., Pallone F. Phenotypes and spontaneous immunoglobulin production in mononuclear cells suspensions isolated from colonic biopsies of patients with mild active and quiescent ulcerative colitis. Gastroenterol Clin Biol. 1991;15(3):194–198. [PubMed] [Google Scholar]
  28. Stanton G. J., Langford M. P., Dianzani F. Virus yield-reduction assay for interferon by titration of Sindbis virus hemagglutinin. Methods Enzymol. 1981;78(Pt A):351–357. doi: 10.1016/0076-6879(81)78141-2. [DOI] [PubMed] [Google Scholar]
  29. Taylor J. L., Grossberg S. E. Recent progress in interferon research: molecular mechanisms of regulation, action, and virus circumvention. Virus Res. 1990 Jan;15(1):1–25. doi: 10.1016/0168-1702(90)90010-9. [DOI] [PubMed] [Google Scholar]
  30. Tsukui K., Miura T., Tokunaga E. Treatment of human peripheral blood leukocytes with proteases does not affect Sendai virus-induced interferon production. Infect Immun. 1984 Mar;43(3):822–824. doi: 10.1128/iai.43.3.822-824.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Weigent D. A., Langford M. P., Smith E. M., Blalock J. E., Stanton G. J. Human B lymphocytes produce leukocyte interferon after interaction with foreign cells. Infect Immun. 1981 May;32(2):508–512. doi: 10.1128/iai.32.2.508-512.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES