Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1995 Jan;99(1):65–69. doi: 10.1111/j.1365-2249.1995.tb03473.x

A role for IL-4 in immunologically mediated enteropathy.

A M Mowat 1, M B Widmer 1
PMCID: PMC1534147  PMID: 7813111

Abstract

A number of clinical enteropathies are associated with a local cell-mediated immune (CMI) response, and experimental evidence indicates that cytokines are responsible for the intestinal pathology. We show here that depletion of IL-4 using MoAb or a soluble form of the IL-4 receptor (IL-4R) prevents the jejunal manifestations of a proliferative form of murine graft-versus-host reaction (GVHR) characterized by crypt hyperplasia and recruitment of intraepithelial lymphocytes (IEL). Depletion of IL-4 did not prevent the appearance of villus atrophy in a destructive model of GVHR, and had no effect on any indices of systemic immunity. These results indicate that IL-4 may play a selective role in mediating proliferative aspects of intestinal immunopathology, and suggest that this cytokine may provide a useful target for immunotherapy.

Full text

PDF
69

Selected References

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

  1. Ballas Z. K., Rasmussen W. Lymphokine-activated killer cells. VII. IL-4 induces an NK1.1+CD8 alpha+beta- TCR-alpha beta B220+ lymphokine-activated killer subset. J Immunol. 1993 Jan 1;150(1):17–30. [PubMed] [Google Scholar]
  2. Borland A., Mowat A. M., Parrott D. M. Augmentation of intestinal and peripheral natural killer cell activity during the graft-versus-host reaction in mice. Transplantation. 1983 Nov;36(5):513–519. doi: 10.1097/00007890-198311000-00009. [DOI] [PubMed] [Google Scholar]
  3. Doutrelepont J. M., Moser M., Leo O., Abramowicz D., Vanderhaegen M. L., Urbain J., Goldman M. Hyper IgE in stimulatory graft-versus-host disease: role of interleukin-4. Clin Exp Immunol. 1991 Jan;83(1):133–136. doi: 10.1111/j.1365-2249.1991.tb05602.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Else K. J., Entwistle G. M., Grencis R. K. Correlations between worm burden and markers of Th1 and Th2 cell subset induction in an inbred strain of mouse infected with Trichuris muris. Parasite Immunol. 1993 Oct;15(10):595–600. doi: 10.1111/pim.1993.15.10.595. [DOI] [PubMed] [Google Scholar]
  5. Fanslow W. C., Clifford K. N., Park L. S., Rubin A. S., Voice R. F., Beckmann M. P., Widmer M. B. Regulation of alloreactivity in vivo by IL-4 and the soluble IL-4 receptor. J Immunol. 1991 Jul 15;147(2):535–540. [PubMed] [Google Scholar]
  6. Garside P., Bunce C., Tomlinson R. C., Nichols B. L., Mowat A. M. Analysis of enteropathy induced by tumour necrosis factor alpha. Cytokine. 1993 Jan;5(1):24–30. doi: 10.1016/1043-4666(93)90020-6. [DOI] [PubMed] [Google Scholar]
  7. Garside P., Felstein M. V., Green E. A., Mowat A. M. The role of interferon alpha/beta in the induction of intestinal pathology in mice. Immunology. 1991 Oct;74(2):279–283. [PMC free article] [PubMed] [Google Scholar]
  8. Garside P., Hutton A. K., Severn A., Liew F. Y., Mowat A. M. Nitric oxide mediates intestinal pathology in graft-vs.-host disease. Eur J Immunol. 1992 Aug;22(8):2141–2145. doi: 10.1002/eji.1830220827. [DOI] [PubMed] [Google Scholar]
  9. Garside P., Reid S., Steel M., Mowat A. M. Differential cytokine production associated with distinct phases of murine graft-versus-host reaction. Immunology. 1994 Jun;82(2):211–214. [PMC free article] [PubMed] [Google Scholar]
  10. Guy-Grand D., Malassis-Seris M., Briottet C., Vassalli P. Cytotoxic differentiation of mouse gut thymodependent and independent intraepithelial T lymphocytes is induced locally. Correlation between functional assays, presence of perforin and granzyme transcripts, and cytoplasmic granules. J Exp Med. 1991 Jun 1;173(6):1549–1552. doi: 10.1084/jem.173.6.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kopf M., Le Gros G., Bachmann M., Lamers M. C., Bluethmann H., Köhler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993 Mar 18;362(6417):245–248. doi: 10.1038/362245a0. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. McCarthy P. L., Jr, Abhyankar S., Neben S., Newman G., Sieff C., Thompson R. C., Burakoff S. J., Ferrara J. L. Inhibition of interleukin-1 by an interleukin-1 receptor antagonist prevents graft-versus-host disease. Blood. 1991 Oct 15;78(8):1915–1918. [PubMed] [Google Scholar]
  15. Mohler K. M., Torrance D. S., Smith C. A., Goodwin R. G., Stremler K. E., Fung V. P., Madani H., Widmer M. B. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol. 1993 Aug 1;151(3):1548–1561. [PubMed] [Google Scholar]
  16. Mowat A. M., Ferguson A. Intraepithelial lymphocyte count and crypt hyperplasia measure the mucosal component of the graft-versus-host reaction in mouse small intestine. Gastroenterology. 1982 Aug;83(2):417–423. [PubMed] [Google Scholar]
  17. Mowat A. M., Hutton A. K., Garside P., Steel M. A role for interleukin-1 alpha in immunologically mediated intestinal pathology. Immunology. 1993 Sep;80(1):110–115. [PMC free article] [PubMed] [Google Scholar]
  18. Mowat A. M., Sprent J. Induction of intestinal graft-versus-host reactions across mutant major histocompatibility antigens by T lymphocyte subsets in mice. Transplantation. 1989 May;47(5):857–863. doi: 10.1097/00007890-198905000-00022. [DOI] [PubMed] [Google Scholar]
  19. Murch S. H., Braegger C. P., Walker-Smith J. A., MacDonald T. T. Location of tumour necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease. Gut. 1993 Dec;34(12):1705–1709. doi: 10.1136/gut.34.12.1705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nestel F. P., Price K. S., Seemayer T. A., Lapp W. S. Macrophage priming and lipopolysaccharide-triggered release of tumor necrosis factor alpha during graft-versus-host disease. J Exp Med. 1992 Feb 1;175(2):405–413. doi: 10.1084/jem.175.2.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ohlsson K., Björk P., Bergenfeldt M., Hageman R., Thompson R. C. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature. 1990 Dec 6;348(6301):550–552. doi: 10.1038/348550a0. [DOI] [PubMed] [Google Scholar]
  22. Piguet P. F. GVHR elicited by products of class I or class II loci of the MHC: analysis of the response of mouse T lymphocytes to products of class I and class II loci of the MHC in correlation with GVHR-induced mortality, medullary aplasia, and enteropathy. J Immunol. 1985 Sep;135(3):1637–1643. [PubMed] [Google Scholar]
  23. Piguet P. F., Grau G. E., Allet B., Vassalli P. Tumor necrosis factor/cachectin is an effector of skin and gut lesions of the acute phase of graft-vs.-host disease. J Exp Med. 1987 Nov 1;166(5):1280–1289. doi: 10.1084/jem.166.5.1280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Umland S. P., Razac S., Nahrebne D. K., Seymour B. W. Effects of in vivo administration of interferon (IFN)-gamma, anti-IFN-gamma, or anti-interleukin-4 monoclonal antibodies in chronic autoimmune graft-versus-host disease. Clin Immunol Immunopathol. 1992 Apr;63(1):66–73. doi: 10.1016/0090-1229(92)90095-6. [DOI] [PubMed] [Google Scholar]
  25. Zurawski G., de Vries J. E. Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today. 1994 Jan;15(1):19–26. doi: 10.1016/0167-5699(94)90021-3. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES