Regulation and Pharmacology of Granulomatous Inflammation

  • Vernon L. Moore
Part of the Infectious Agents and Pathogenesis book series (IAPA)


Granulomatous inflammation consists of collections of macrophages, epithelioid macrophages, and sometimes lymphocytes around a nidus such as the tubercle bacillus, Schistosoma mansoni eggs, or other foreign material (usually particulate). This type of inflammation can be classified according to cell type, organization, whether it exhibits low turnover or high turnover, or whether it is nonimmunologic (foreign body) or immune based. All these aspects have been described in recent reviews.1,2 An important example of granulomatous inflammation is tuberculosis, for which the pathology has also been extensively described. In tuberculosis, the development of granulomatous inflammation is a host response to the tubercle bacillus that is probably beneficial in augmenting the killing of Mycobacterium tuberculosis and in sequestrating the organisms to prevent dissemination. However, in tuberculosis as well as other granulomatous diseases, granulomatous inflammation is clearly a two- edged sword, since it also results in extensive inflammation, necrosis, calcification, and fibrosis. The maximal development of granulomatous inflammation in tuberculosis is probably dependent on inflammation induced by the development of delayed hypersensitivity to antigens of the tubercle bacillus. Indeed, it is this immune response that is primarily responsible for producing activated macrophages responsible for controlling the growth and pathogenesis of M. tuberculosis.


Idiopathic Pulmonary Fibrosis Migration Inhibition Factor Granuloma Formation Granulomatous Inflammation Schistosoma Mansoni 
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  1. 1.
    Adams, D. O., 1976, The granulomatous inflammatory response-A review, Am. J. Pathol. 84:164–191.PubMedGoogle Scholar
  2. 2.
    Garrett, K. C., Richerson, H. B., Hunninghake, G. W., 1984, Pathogenesis of granulomatous lung diseases. II. Mechanisms of granuloma formation, Am. Rev. Respir. Dis. 130:447–483.Google Scholar
  3. 3.
    Boros, D. L., 1978, Granulomatous inflammation, Prog. Allergy 24:184–267.Google Scholar
  4. 4.
    Warren, K. S., 1980, The relevance of schistosomiasis, N. Engl. J. Med. 303:203–206.PubMedCrossRefGoogle Scholar
  5. 5.
    Moore, V. L., Schrier, D. J. ,Sternick, J. L., and Allen, E. M., 1980, Genetic control of granulomatous inflammation, in: Basic and Clinical Aspects of Granulomatous Diseases (D. Boros and T. Yoshida, eds.), pp. 201–214, Elsevier-North-Holland, Amsterdam.Google Scholar
  6. 6.
    Yamamoto, K., and Kakinuma, M., 1978, Genetic control of granuloma response to oil-associated BCG cell wall vaccine in mice, Microbiol. Immunol. 22:335–348.PubMedGoogle Scholar
  7. 7.
    Skamene, E., Gros, P., Forget, A., Kongshavn, P. A. L., St. Gharles, C., and Taylor, B. A. ,1982, Genetic regulation of resistance to intracellular pathogens, Nature (Lond.) 297:506–509.CrossRefGoogle Scholar
  8. 8.
    Phillips, S. M., DiConza, J. J., Gold, J. A., and Reid, W. A., 1977, Schistosomiasis in the congenitally athymic (nude) mouse. I. Thymic dependency of eosinophilic, granuloma formation and host morbidity, J. Immunol. 118:594–599.PubMedGoogle Scholar
  9. 9.
    Chensue, S. W., Boros, D. L., and David, C. S., 1980, Regulation of granulomatous inflammation in murine schistosomiasis. In vitro characterization of T lymphocyte subsets involved in the production and suppression of migration inhibition factor, J. Exp. Med. 151:1398–1412.PubMedCrossRefGoogle Scholar
  10. 10.
    Chensue, S. W., Wellhausen, S. R., and Boros, D. L., 1981, Modulation of granulomatous hypersensitivity. II. Participation of Lyl+ and Ly2 + T lymphocytes in the suppression of granuloma formation and lymphokine production in Schistosoma man- .sora-infected mice, J. Immunol. 127:363–367.PubMedGoogle Scholar
  11. 11.
    Colley, D. G., 1976, Adoptive suppression of granuloma formation, J. Exp. Med. 143:696–700.PubMedCrossRefGoogle Scholar
  12. 12.
    Colley, D. G., Lewis, F. A., and Todd, C. W., 1979, Adoptive suppression of granuloma formation by T lymphocytes and by lymphoid cells sensitive to cyclophosphamide, Cell. Immunol. 46: 192–196.PubMedCrossRefGoogle Scholar
  13. 13.
    Colley, D. G., 1981, T lymphocytes that contribute to the immunoregulation of granuloma formation in chronic murine schistosomiasis, J. Immunol. 126: 1465–1468.PubMedGoogle Scholar
  14. 14.
    Green, W. F., and Colley, D. G., 1981, Modulation of Schistosoma mansoni egg-induced granuloma formation: I-J restriction of T cell-mediated suppression in a chronic parasitic infection, Proc. Natl. Acad. Sci. USA 78: 1152–1156.PubMedCrossRefGoogle Scholar
  15. 15.
    Powell, M. R., and Colley, D. G., 1985, Demonstration of splenic auto-Anti-idiotypic plaque-forming cells in mice infected with Schistosoma mansoni, J. Immunol. 134:4140– 4145.PubMedGoogle Scholar
  16. 16.
    Aune, T. M., Freeman, C. L., Jr., and Colley, D. G., 1985, Production of the lymphokine soluble immune response suppressor (SIRS) during chronic experimental schistosomiasis mansoni, J. Immunol. 135:2768–2771.PubMedGoogle Scholar
  17. 17.
    Myrvik, Q. N., Leake, E. S., and Fariss, B., 1961, Studies on pulmonary alveolar macrophages from the normal rabbit: A technique to procure them in a high state of purity, J. Immunol. 86: 128–132.PubMedGoogle Scholar
  18. 18.
    Myrvik, Q. N., Leake, E. S., and Oshima, S., 1962, A study of macrophages and epithelioid-like cells from granulomatous (BCG-induced) lungs of rabbits, J. Immunol. 89:745–751.PubMedGoogle Scholar
  19. 19.
    Kawata, H., Myrvik, Q. N., and Leake, E. S., 1964, Dissociation of tuberculin hypersensitivity as mediator for an accelerated pulmonary granulomatous response in rabbits, J. Immunol. 93:433–438.PubMedGoogle Scholar
  20. 20.
    Moore, V. L., Myrvik, Q. N., and Leake, E. S., 1973, Specificity of a BCG-induced pulmonary granulomatous response in rabbits, Infect. Immun. 7:743–746.PubMedGoogle Scholar
  21. 21.
    Galindo, B., and Myrvik, Q. N., 1970, Migratory response of granulomatous alveolar cells from BCG-sensitized rabbits, J. Immunol. 105:227–237.PubMedGoogle Scholar
  22. 22.
    Moore, V. L., and Myrvik, Q. N., 1974, Inhibition of normal rabbit alveolar macrophages by factor(s) resembling migration inhibition factor, J. Reticuloendothel. Soc. 16:21–26.PubMedGoogle Scholar
  23. 23.
    Allen, E. M., Moore, V. L., and Stevens, J. O., 1977, Strain variation in BCG-induced chronic pulmonary inflammation in mice. I. Basic model and possible genetic control by non-H-2 genes, J. Immunol. 119:343–347.PubMedGoogle Scholar
  24. 24.
    Sternick, J. L., Allen, E. M., Ripani, L. M., Schrier, D. J., and Moore, V. L., 1981, BCG-induced granulomatous pulmonary inflammation and splenomegaly in mice: A T cell-dependent response, Cell. Immunol. 65:211–220.CrossRefGoogle Scholar
  25. 25.
    Sternick, J. L., Schrier, D. J., Moore, V. L., 1983, Genetic control of BCG-induced granulomatous inflammation in mice, Exp. Lung Res. 5:217–228.PubMedCrossRefGoogle Scholar
  26. 26.
    Moore, V. L., Mondloch, V. M., Pedersen, G. M., Schrier, D. J., and Allen, E. M., 1981, Strain variation in BCG-induced chronic pulmonary inflammation in mice: Control by a cyclophosphamide-sensitive thymus-derived suppressor cell, J. Immunol. 127:339– 342.PubMedGoogle Scholar
  27. 27.
    Yamamoto, K., Kato, K., Kakinuma, M., and Brehmer, W., 1982, Cellular regulation of lung granuloma formation and delayed-type hypersensitivity induced with BCG cell walls. Further evidence of involvement of cellular immunity in lung granuloma formation, Zentralbl. Bakteriol. Mikrobiol. Hyg. [A] 251:357–368.Google Scholar
  28. 28.
    Allen, E. M., and Moore, V. L., 1979, Suppression of phytohemagglutinin and lipopolysaccharide responses in mouse spleen cells by bacillus Calmette-Guérin, J. Reticuloendothel. Soc. 26:349–356.PubMedGoogle Scholar
  29. 29.
    Allen, E. M., Sternick, J. L., Schrier, D. J., and Moore, V. L., 1981, BCG-induced chronic pulmonary inflammation and splenomegaly in mice: suppression of PHA-induced proliferation, delayed hypersensitivity to sheep erythrocytes, and chronic pulmonary inflammation by soluble factors from adherent spleen cells, Cell. Immunol. 58:61–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Schrier, D. J., Allen, E. M., and Moore, V. L., 1980, BCG-induced macrophage suppression in mice: Suppression of specific and non-specific antibody-mediated and cellular immunologic responses, Cell. Immunol. 56:347–356.PubMedCrossRefGoogle Scholar
  31. 31.
    Schrier, D. J., Sternick, J. L., Allen, E. M., and Moore, V. L., 1982, Immunogenetics of BCG-induced anergy in mice: Control by genes linked to the Igh complex, J. Immunol. 128:1466–1469.PubMedGoogle Scholar
  32. 32.
    Callis, A. H., Schrier, D. J., David, C. S., and Moore, V. L., 1983, Immunogenetics of BCG-induced anergy in mice. Control by Igh- and H-2-linked genes, Immunology 49:509–516.Google Scholar
  33. 33.
    Kakinuma, M., Onoé, K., Yasumizu, R., and Yamamoto, K., 1983, Strain differences in lung granuloma formation in response to a BCG cell-wall vaccine in mice. Failure of antigen presentation by low-responder macrophages, Immunology 50:423–431.PubMedGoogle Scholar
  34. 34.
    Kato, K., Yamamoto, K., Okuyama, H., and Kimura, T., 1984, Microbicidal activity and marphological characteristics of lung macrophages in Mycobacterium bovis BCG cell wall-induced lung granuloma in mice, Infect. Immun. 45:325–331.PubMedGoogle Scholar
  35. 35.
    Kakinuma, M., Onoé, K., Okada, M., Kimura, T., Kato, K., Okuyama, H., Morikawa, K., and Yamamoto, K., 1981, Failure of C3H mice to develop lung granuloma after intravenous injection of BCG cell wall vaccine. Demonstration of a defect in lymphoid cells, Immunology 43:1–9.PubMedGoogle Scholar
  36. 36.
    Kakinuma, M., and Yamamoto, K., 1985, Strain differences in lung granuloma formation in response to a BCG cell-wall vaccine in mice. Demonstration of two types of low responders, Immunology 55:91–95.PubMedGoogle Scholar
  37. 37.
    Bourassa, D., Forget, A., Pelletier, M., Skamene, E., and Turcotte, R., 1985, Cellular immune response to Mycobacterium bovis (BCG) in genetically-susceptible and resistant congenic mouse strains, Clin. Exp. Immunol. 62:31–38.PubMedGoogle Scholar
  38. 38.
    Webster, L. T., Jr., Butterworth, A. E., Mahmoud, A. A. F., Mngola, E. N., and Warren, K. S., 1975, Suppression of delayed hypersensitivity in schistosome-infected patients by niridazole, N. Engl. J. Med. 292:1144–1147.PubMedCrossRefGoogle Scholar
  39. 39.
    Daniels, J. C., Fajordo, I., and David, J. R., 1975, Two stages in lymphocyte mediator production by differential susceptibility to blockade using niridazole, Proc. Natl. Acad. Sci. USA 72:4569–4597.PubMedCrossRefGoogle Scholar
  40. 40.
    Tracy, J. W., Kazura, J. W., and Webster, L. T., Jr., 1982, Suppression of cell-mediated immune responses in vivo and in vitro by l-thiocarbamoyl-2-imidazolidinone, .Immu-nopharmacology 4: 187–200.Google Scholar
  41. 41.
    Gautman, S. C., Scissors, D. L., and Webster, L. T., Jr., 1982, Further observations on the effects of l-thiocarbamoyl-2-imidazolidinone (TCI) on cell-mediated immunity, Immunopharmacology 4:201–212.PubMedCrossRefGoogle Scholar
  42. 42.
    Goodwin, J. S., and Ceuppens, J., 1983, Regulation of the immune response by prostaglandins, J. Clin. Immunol. 3:295–314.PubMedCrossRefGoogle Scholar
  43. 43.
    Claman, H. N., 1984, Anti-inflammatory effects of conticosteroids, Clin. Immunol. Allergy 4:317–329.Google Scholar
  44. 44.
    Nakamura, H., Mizushima, Y., Seto, Y., Motoyoshi, S., and Kadokawa, T., 1985, Dexamethasone fails to produce antipyretic and analgesic actions in experimental animals, Agents Actions 16:542–547.PubMedCrossRefGoogle Scholar
  45. 44.
    Lipsky, P. E., 1983, Remission-inducing therapy in rheumatoid arthritis, Am. J. Med. 75 (suppl. 48):40–49.PubMedCrossRefGoogle Scholar
  46. 45.
    Shevach, E. M., 1985, The effects of cyclosporin A on the immune system, Annu. Rev. Immunol. 3:397–423.PubMedCrossRefGoogle Scholar
  47. 46.
    Rocklin, R. E., 1982, Modulation of inflammatory and immune responses by histamine, in: Immunopharmacology (P. Sirois and M. Rola-Pleszczynski eds.), pp. 49–74, Elsevier Biomedical Press, New York.Google Scholar
  48. 47.
    Silverstein, E., Friedland, J. ,Lyons, H. A. ,and Gourin, A. ,1976, Markedly elevated angiotensin-converting enzyme in lymph nodes containing non-necrotizing gran-ulomous in sarcoidosis, Proc. Natl. Acad. Sci. USA 73:2137–2141.PubMedCrossRefGoogle Scholar
  49. 48.
    Schrier, D. J., Ripani, L. M., Katzenstein, A. L., and Moore, V. L., 1982, Role of angiotensin-converting enzyme in Bacille Calmette-Geúrin-induced granulomatous inflammation. Increased angiotensin-converting enzyme levels in lung lavage and suppression of inflammation with captopril, J. Clin. Invest. 69:651–657.PubMedCrossRefGoogle Scholar
  50. 49.
    Weinstock, J. V., Ehrinpreis, M. N., Boros, D. L., and Gee, J. B., 1981, Effect of SQ 14225, an inhibitor of angiotensin 1-converting enzyme, on the granulomatous response to Schistosoma mansoni eggs in mice, J. Clin. Invest. 67:931–936.PubMedCrossRefGoogle Scholar
  51. 50.
    Kunkel, S. L., Chensue, S. W., Mouton, C., and Higashi, G. I., 1984, Role of lipoxy-genase products in murine pulmonary granuloma formation, J. Clin. Invest. 74:514– 524.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Vernon L. Moore
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyMerck Sharp & Dohme Research LaboratoriesRahwayUSA

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