Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1988 Jun;131(3):530–538.

Sex hormones modulate the response of pulmonary perivascular inflammation to cyclophosphamide therapy in MRL/MpJ-lpr/lpr mice.

W N McKenzie Jr 1, E V Sunderrajan 1, J L Kavanaugh 1, S Braun 1, L Ansbacher 1, S E Walker 1
PMCID: PMC1880696  PMID: 3381881

Abstract

Responses of pulmonary perivascular infiltrates to immunosuppressive therapy with cyclophosphamide (CY) were evaluated in the MRL/MpJ-lpr/lpr (MRL/1) mouse, a model for the study of systemic lupus erythematosus. Male and female mice were divided into the following groups: controls injected with saline; intact mice receiving CY; castrated CY-treated mice; castrated, hormone implanted, CY-treated mice. CY treatment began at 30 days of age and animals were killed at 60 days of age. Lungs were fixed-inflated to 26 cm H2O pressure with glutaraldehyde-formaldehyde fixative. The pulmonary perivascular response to immunosuppressive therapy was graded depending on the extent of infiltrates surrounding 15 pulmonary vessels per animal. Intact males treated with CY alone had almost complete clearing of perivascular infiltrates, whereas intact females did not respond to therapy. Castrated CY-treated males showed a decreased response to CY compared to intact CY-treated males. Castrated, estradiol-implanted males had no response to CY therapy. Estradiol interfered with the therapeutic response to CY in male MRL/1 mice.

Full text

PDF
530

Images in this article

532p532-a
on p.532
533Figure 2
on p.533
534p534-a
on p.534
535Figure 3
on p.535

Selected References

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

  1. Ahmed A. R., Hombal S. M. Cyclophosphamide (Cytoxan). A review on relevant pharmacology and clinical uses. J Am Acad Dermatol. 1984 Dec;11(6):1115–1126. doi: 10.1016/s0190-9622(84)80193-0. [DOI] [PubMed] [Google Scholar]
  2. Andrews B. S., Eisenberg R. A., Theofilopoulos A. N., Izui S., Wilson C. B., McConahey P. J., Murphy E. D., Roths J. B., Dixon F. J. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. doi: 10.1084/jem.148.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ansar Ahmed S., Dauphinee M. J., Talal N. Effects of short-term administration of sex hormones on normal and autoimmune mice. J Immunol. 1985 Jan;134(1):204–210. [PubMed] [Google Scholar]
  4. Brick J. E., Walker S. E., Wise K. S. Hormone control of autoantibodies to calf thymus nuclear extract (CTE) and DNA in MRL-lpr and MRL-+/+ mice. Clin Immunol Immunopathol. 1988 Jan;46(1):68–81. doi: 10.1016/0090-1229(88)90007-4. [DOI] [PubMed] [Google Scholar]
  5. Brick J. E., Wilson D. A., Walker S. E. Hormonal modulation of responses to thymus-independent and thymus-dependent antigens in autoimmune NZB/W mice. J Immunol. 1985 Jun;134(6):3693–3698. [PubMed] [Google Scholar]
  6. Churg A., Franklin W., Chan K. L., Kopp E., Carrington C. B. Pulmonary hemorrhage and immune-complex deposition in the lung. Complications in a patient with systemic lupus erythematosus. Arch Pathol Lab Med. 1980 Jul;104(7):388–391. [PubMed] [Google Scholar]
  7. Cohen J. L., Jao J. Y. Enzymatic basis of cyclophosphamide activation by hepatic microsomes of the rat. J Pharmacol Exp Ther. 1970 Aug;174(2):206–210. [PubMed] [Google Scholar]
  8. Elliott M. L., Kuhn C. Idiopathic pulmonary hemosiderosis. Ultrastructural abnormalities in the capillary walls. Am Rev Respir Dis. 1970 Dec;102(6):895–904. doi: 10.1164/arrd.1970.102.6.895. [DOI] [PubMed] [Google Scholar]
  9. Feeney L., Wissig S. L. A biochemical and radioautographic analysis of protein secretion by thyroid lobes incubated in vitro. J Cell Biol. 1972 May;53(2):510–522. doi: 10.1083/jcb.53.2.510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gross M., Esterly J. R., Earle R. H. Pulmonary alterations in systemic lupus erythematosus. Am Rev Respir Dis. 1972 Apr;105(4):572–577. doi: 10.1164/arrd.1972.105.4.572. [DOI] [PubMed] [Google Scholar]
  11. Hayakawa T., Kanai N., Yamada R., Kuroda R., Higashi H., Mogami H., Jinnai D. Effect of steroid hormone on activation of Endoxan (cyclophosphamide). Biochem Pharmacol. 1969 Jan;18(1):129–135. doi: 10.1016/0006-2952(69)90017-3. [DOI] [PubMed] [Google Scholar]
  12. Howie J. B., Helyer B. J. The immunology and pathology of NZB mice. Adv Immunol. 1968;9:215–266. doi: 10.1016/s0065-2776(08)60444-7. [DOI] [PubMed] [Google Scholar]
  13. Hunninghake G. W., Fauci A. S. Pulmonary involvement in the collagen vascular diseases. Am Rev Respir Dis. 1979 Mar;119(3):471–503. doi: 10.1164/arrd.1979.119.3.471. [DOI] [PubMed] [Google Scholar]
  14. Inoue T., Kanayama Y., Ohe A., Kato N., Horiguchi T., Ishii M., Shiota K. Immunopathologic studies of pneumonitis in systemic lupus erythematosus. Ann Intern Med. 1979 Jul;91(1):30–34. doi: 10.7326/0003-4819-91-1-30. [DOI] [PubMed] [Google Scholar]
  15. Kuhn C. Systemic lupus erythematosus in a patient with ultrastructural lesions of the pulmonary capillaries previously reported in the review as due to idiopathic pulmonary hemosiderosis. Am Rev Respir Dis. 1972 Dec;106(6):931–932. doi: 10.1164/arrd.1972.106.6.931a. [DOI] [PubMed] [Google Scholar]
  16. Lahita R. G., Bradlow H. L., Kunkel H. G., Fishman J. Increased 16 alpha-hydroxylation of estradiol in systemic lupus erythematosus. J Clin Endocrinol Metab. 1981 Jul;53(1):174–178. doi: 10.1210/jcem-53-1-174. [DOI] [PubMed] [Google Scholar]
  17. Matthay R. A., Schwarz M. I., Petty T. L., Stanford R. E., Gupta R. C., Sahn S. A., Steigerwald J. C. Pulmonary manifestations of systemic lupus erythematosus: review of twelve cases of acute lupus pneumonitis. Medicine (Baltimore) 1975 Sep;54(5):397–409. doi: 10.1097/00005792-197509000-00003. [DOI] [PubMed] [Google Scholar]
  18. Melez K. A., Boegel W. A., Steinberg A. D. Therapeutic studies in New Zealand mice. VII. Successful androgen treatment of NZB/NZW F1 females of different ages. Arthritis Rheum. 1980 Jan;23(1):41–47. doi: 10.1002/art.1780230108. [DOI] [PubMed] [Google Scholar]
  19. Reidenberg M. M., Case D. B., Drayer D. E., Reis S., Lorenzo B. Development of antinuclear antibody in patients treated with high doses of captopril. Arthritis Rheum. 1984 May;27(5):579–581. doi: 10.1002/art.1780270516. [DOI] [PubMed] [Google Scholar]
  20. Roubinian J., Talal N., Siiteri P. K., Sadakian J. A. Sex hormone modulation of autoimmunity in NZB/NZW mice. Arthritis Rheum. 1979 Nov;22(11):1162–1169. doi: 10.1002/art.1780221102. [DOI] [PubMed] [Google Scholar]
  21. Shear H. L., Wofsy D., Talal N. Effects of castration and sex hormones on immune clearance and autoimmune disease in MRL/Mp-lpr/lpr and MRL/Mp-+/+ mice. Clin Immunol Immunopathol. 1983 Mar;26(3):361–369. doi: 10.1016/0090-1229(83)90120-4. [DOI] [PubMed] [Google Scholar]
  22. Smith H. R., Chused T. M., Steinberg A. D. Cyclophosphamide-induced changes in the MRL-lpr/lpr mouse: effects upon cellular composition, immune function, and disease. Clin Immunol Immunopathol. 1984 Jan;30(1):51–61. doi: 10.1016/0090-1229(84)90006-0. [DOI] [PubMed] [Google Scholar]
  23. Sunderrajan E. V., McKenzie W. N., Lieske T. R., Kavanaugh J. L., Braun S. R., Walker S. E. Pulmonary inflammation in autoimmune MRL/Mp-lpr/lpr mice. Histopathology and bronchoalveolar lavage evaluation. Am J Pathol. 1986 Aug;124(2):353–362. [PMC free article] [PubMed] [Google Scholar]
  24. Walker S. E., Bole G. G., Jr Selective suppression of autoantibody responses in NZB/NZW mice treated with long-term cyclophosphamide. Arthritis Rheum. 1975 May-Jun;18(3):265–272. doi: 10.1002/art.1780180312. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES