Cell/Cytokine Interactions

  • David H. Broide


Cytokines provide an important local mechanism for inflammatory cells at sites of allergic inflammation to communicate with each other in orchestrating the inflammatory response. Cytokines regulate a number of cellular functions important to allergic inflammation, including the regulation of immunoglobulin E (IgE) synthesis, the regulation of the expression of adhesion molecules by endothelium, and the regulation of inflammatory cell function (1). Our understanding of the relative importance of individual cytokines to allergic inflammation has been advanced by the cloning of cytokines and cytokine receptors, the elucidation of the crystal structure of cytokines suggesting important ligand binding sites, and in vitro functional studies using recombinant cytokines and individual cell types important to allergic function (i.e., mast cells, eosinophils, T-cells, B-cells, endothelium, epithelium). We will review cell/cytokine interactions in the context of these studies, focusing particularly on cytokine interactions with eosinophils, as well as review important advances in understanding the in vivo role of individual cytokines in studies using cytokine transgenic mice (mice over-expressing a particular cytokine) (2) or cytokine knockout mice (mice deficient in a particular cytokine) (3) (Table 1).


Knockout Mouse Vascular Cell Adhesion Molecule Airway Hyperresponsiveness Allergic Inflammation Eosinophilic Inflammation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Broide DH (1995) Cytokines and adhesion molecules in asthma. Curr Allergy Clin Immunol 8: 19–22.Google Scholar
  2. 2.
    Hanahan D (1989) Transgenic mice as probes into complex systems. Science 246: 1265–1275.PubMedCrossRefGoogle Scholar
  3. 3.
    Lewis J, Yang B, Detloff P, Smithies O (1996) Gene modification via “plug and socket” gene targeting. J Clin Invest 97: 3–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Nicola NA (1995) Structural aspects of cytokine/receptor interactions. Ann NY Acad Sci 766: 253.PubMedCrossRefGoogle Scholar
  5. 5.
    Ihle JN (1995) Cytokine receptor signalling. Nature 377: 591.PubMedCrossRefGoogle Scholar
  6. 6.
    Schall TJ, Bacon KB (1994) Chemokines, leukocyte trafficking, and inflammation. Curr Opin Immunol 6: 8651–873.CrossRefGoogle Scholar
  7. 7.
    Bochner BS, Klunk DA, Sterbinsky SA, Coffman RL, Schleimer RP (1995) Interleukin-13 selectively induces vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells. J Immunol 154: 799–803.PubMedGoogle Scholar
  8. 8.
    Tepper RI, Levinson DA, Stanger BZ, et al. (1990) IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice. Cell 62: 457–467.PubMedCrossRefGoogle Scholar
  9. 9.
    Burstein HJ, Tepper RI, Leder P, Abbas AK (1991) Humoral immune functions in IL-4 transgenic mice. J Immunol 147: 2950–2956.PubMedGoogle Scholar
  10. 10.
    Dent LA, Strath M, Mellor AL, Sanderson CJ (1990) Eosinophil in transgenic mice expressing interleukin 5. J Exp Med 172: 1425–1431.PubMedCrossRefGoogle Scholar
  11. 11.
    Tominaga A, Takaki S, Koyama N, et al. (1991) Transgenic mice expressing a B cell growth and differentiation factor gene (Interleukin 5) develop eosinophilia and autoantibody production. J Exp Med 173: 429–437.PubMedCrossRefGoogle Scholar
  12. 12.
    Elliott MJ, Strasser A, Metcalf D (1991) Selective up-regulation of macrophage function in granulocyte-macrophage colony-stimulating factor transgenic mice. J Immunol 147: 2957–2963.PubMedGoogle Scholar
  13. 13.
    Stanley E, Lieschke GJ, Grail D, et al. (1994) Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc Natl Acad Sci USA 90: 770–774.Google Scholar
  14. 14.
    Huang S, Hendriks W, Althage A, et al. (1993) Immune response in mice that lack the interferon-y receptor. Science 250: 1742–1745.CrossRefGoogle Scholar
  15. 15.
    Dalton DK, Pitts-Meek S, Keshav S, et al. (1993) Multiple defects of immune cell function in mice with disrupted interferon-y genes. Science 259: 1739–1742.PubMedCrossRefGoogle Scholar
  16. 16.
    Amiri P, Haak-Frendscho M, Robbins K, et al. (1994) Anti-immunoglobulin E treatment decreases worm burden and egg production in Schistosoma mansoni-infected norma and interferon-y knockout mice. J Exp Med 180: 43–51.PubMedCrossRefGoogle Scholar
  17. 17.
    Kuhn R, Rajewsky K, Muller W (1991) Generation and analysis of interleukin-4 deficient mice. Science 254: 707–710.PubMedCrossRefGoogle Scholar
  18. 18.
    Kopf M, LeGros G, Bachmann, et al. (1993) Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 362: 245–248.PubMedCrossRefGoogle Scholar
  19. 19.
    Brusselle G, Kips J, Joos G, et al. (1995) Allergen-induced airway inflammation and bronchial responsiveness in wild-type and interleukin-4-deficient mice. Am J Respir Cell Mol Biol 12: 254–259.PubMedGoogle Scholar
  20. 20.
    Coyle AJ, Le Gros G, Bertrand C, et al. (1995) Interleukin-4 required for the induction of lung Th2 mucosal immunity. Am J Respir Cell Mol Biol 13: 54–59.PubMedGoogle Scholar
  21. 21.
    Lukacs MW, Strieter RM, Chensue SW, and Kunkel SL (1994) IL-4 dependent eosinophil infiltration in a murine mouse model of asthma. Am J Respir Cell Mol Biol 10: 526–533.PubMedGoogle Scholar
  22. 22.
    Foster PS, Hogan SP, Ramsay AJ, et al. (1996) Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity and lung damage in a mouse asthma model. J Exp Med 183: 195–201.PubMedCrossRefGoogle Scholar
  23. 23.
    Corry DB, Folkesson HG, Warnock ML, et al. (1996) Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J Exp Med 183: 109–117.PubMedCrossRefGoogle Scholar
  24. 24.
    Drazen JM, Arm JP, Austen KF (1996) Sorting out the cytokines of asthma. J Exp Med 183: 1–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Finkelman FD, Madden KB, Cheever AW, et al. (1994) Effects of interleukin-12 on immune responses and host protection in mice infected with intestinal nematode parasites. J Exp Med 179: 1563–1572.PubMedCrossRefGoogle Scholar
  26. 26.
    Gavett SH, O’Hearn DJ, Li X, et al. (1995) Interleukin 12 inhibits antigen-induced airway hyper-responsiveness, inflammation, and Th2 cytokine expression in mice. J Exp Med 182: 1527–1536.PubMedCrossRefGoogle Scholar
  27. 27.
    Sriramarao P, Von Andrian UH, Butcher EC, et al. (1994) a4131, integrin and L-selectin mediate eosinophil rolling at physiological shear rates in vivo. J Immunol 153: 4238–4246.Google Scholar
  28. 28.
    Sung KLP, Yang L, Elices M, et al. (1996) GM-CSF regulates the functional adhesive state of VLA-4 expressed by eosinophils. J Immunol 158: 919–927.Google Scholar
  29. 29.
    Sriramarao P, Broide DH (1996) Differential regulation of eosinophil adhesion under conditions of flow in vivo. Ann NY Acad Sci 796: 218–225.PubMedCrossRefGoogle Scholar
  30. 30.
    Broide DH Humber D Sullivan S, et al. (1996) Inhibition of eosinophil rolling and recruitment in P-selectin and ICAM deficient mice. Blood. In Press.Google Scholar
  31. 31.
    Bullard DC, Qin L, Lorenzo I, et al. (1995) P-selectin/ICAM-1 double mutant mice: acute emigration of neutrophils into the peritoneum is completely absent but is normal into pulmonary alveoli. J Clin Invest 95: 1782PubMedCrossRefGoogle Scholar
  32. 32.
    Sriramarao P, CR, Norton P, Borgstrom R, DiScipio BA, Wolitzky DH, Broide (1996) E-selectin preferentially supports neutrophil but not eosinophil rolling under conditions of flow in vitro and in vivo. J Immunol 157: 4672–4680.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • David H. Broide

There are no affiliations available

Personalised recommendations