Abstract
The effect of oestrogen or anti-oestrogen administration on gross pathology and in vitro cell-mediated immune responses to homologous IgG, native and denatured interstitial collagens and PPD was studied in an IgG-induced rabbit model of immune synovitis. During induction of synovitis, rabbits were administered oestradiol valerate (0.075 mg/kg/day) or tamoxifen, an anti-oestrogen (2.0 mg/kg/day, high dose or 0.5 mg/kg/day, low dose) or placebo injections. Low dose tamoxifen administration was associated with significant improvement P less than 0.05 in immune synovitis with regard to gross pathology, when compared to placebo and the oestradiol treatment group. High dose tamoxifen treatment was not associated with significant improvement in observed synovitis. With regard to cell-mediated immune responses, spleen cells derived from immune synovitis rabbits were observed to increase 3H-thymidine uptake on incubation with native or denatured homologous collagens. Modulation of these immune responses to antigens was observed in anti-oestrogen treated rabbits with immune synovitis. In vitro cell-mediated immune responses to denatured type I, II and III collagens, PPD, as well as native type II and III collagens were not observed in the low dose tamoxifen treatment group. However, in vitro immune responses to these antigens were observed in spleen cell cultures from immune synovitis rabbits treated with either high dose tamoxifen or oestradiol valerate. The data suggest that in vivo anti-oestrogen administration can modulate the in vitro cell-mediated immune response to connective tissue constituents observed in immune synovitis. Concomitant with reduced immune responses is a significant reduction in the observed lesions of the inflammatory response.
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Selected References
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- Bulger W. H., Kupfer D. Induction of uterine ornithine decarboxylase (ODC) by antiestrogens. Inhibition of estradiol-mediated induction of ODC: a possible mechanism of action of antiestrogens. Endocr Res Commun. 1976;3(3-4):209–218. doi: 10.3109/07435807609056901. [DOI] [PubMed] [Google Scholar]
- Chung E., Miller E. J. Collagen polymorphism: characterization of molecules with the chain composition (alpha 1 (3)03 in human tissues. Science. 1974 Mar;183(130):1200–1201. doi: 10.1126/science.183.4130.1200. [DOI] [PubMed] [Google Scholar]
- Danel L., Souweine G., Monier J. C., Saez S. Specific estrogen binding sites in human lymphoid cells and thymic cells. J Steroid Biochem. 1983 May;18(5):559–563. doi: 10.1016/0022-4731(83)90131-0. [DOI] [PubMed] [Google Scholar]
- Endler A. T., Zielinski C., Menzel E., Smolen J. S., Schwägerl W., Endler M., Eberl R., Frank O., Steffen C. Leucocyte migration inhibition with collagen type I and collagen type III in rheumatoid arthritis and degenerative joint diseases. Z Rheumatol. 1978 Mar-Apr;37(3-4):87–92. [PubMed] [Google Scholar]
- Ezaki T., Nawa Y., Hayama T., Yamaguchi K., Kotani M. Modulation of the immune responses against SRBC after oestriol treatment in mice. Clin Exp Immunol. 1982 Apr;48(1):239–243. [PMC free article] [PubMed] [Google Scholar]
- Fathman C. G., Small M., Herzenberg L. A., Weissman I. L. Thymus cell maturation. II. Differentiation of three "mature" subclasses in vivo. Cell Immunol. 1975 Jan;15(1):109–128. doi: 10.1016/0008-8749(75)90169-0. [DOI] [PubMed] [Google Scholar]
- Gay S., Miller E. J. Characterization of lens capsule collagen: evidence for the presence of two unique chains in molecules derived from major basement membrane structures. Arch Biochem Biophys. 1979 Dec;198(2):370–378. doi: 10.1016/0003-9861(79)90509-5. [DOI] [PubMed] [Google Scholar]
- Goldberg V. M., Lance E. M., Davis P. Experimental immune synovitis in the rabbit. Relative roles of cell mediated and humoral immunity. Arthritis Rheum. 1974 Nov-Dec;17(6):993–1005. doi: 10.1002/art.1780170612. [DOI] [PubMed] [Google Scholar]
- Horwitz K. B., McGuire W. L. Nuclear mechanisms of estrogen action. Effects of estradiol and anti-estrogens on estrogen receptors and nuclear receptor processing. J Biol Chem. 1978 Nov 25;253(22):8185–8191. [PubMed] [Google Scholar]
- Koseki Y., Zava D. T., Chamness G. C., McGuire W. L. Estrogen receptor translocation and replenishment by the antiestrogen tamoxifen. Endocrinology. 1977 Oct;101(4):1104–1110. doi: 10.1210/endo-101-4-1104. [DOI] [PubMed] [Google Scholar]
- Kresina T. F., Miller E. J. Isolation and characterization of basement membrane collagen from human placental tissue. Evidence for the presence of two genetically distinct collagen chains. Biochemistry. 1979 Jul 10;18(14):3089–3097. doi: 10.1021/bi00581a028. [DOI] [PubMed] [Google Scholar]
- Krzych U., Strausser H. R., Bressler J. P., Goldstein A. L. Effects of sex hormones on some T and B cell functions, evidenced by differential immune expression between male and female mice and cyclic pattern of immune responsiveness during the estrous cycle in female mice. Am J Reprod Immunol. 1981;1(2):73–77. doi: 10.1111/j.1600-0897.1981.tb00020.x. [DOI] [PubMed] [Google Scholar]
- Kurl R. N., Borthwick N. M. Clomiphene and tamoxifen action in the rat uterus. J Endocrinol. 1980 Jun;85(3):519–524. doi: 10.1677/joe.0.0850519. [DOI] [PubMed] [Google Scholar]
- Migliaccio A., Auricchio F. Hormone binding of estradiol-17 beta receptor: evidence for its regulation by cytoplasmic phosphorylation and nuclear dephosphorylation. Prevention of dephosphorylation by antiestrogens. J Steroid Biochem. 1981 Dec;15:369–373. doi: 10.1016/0022-4731(81)90299-5. [DOI] [PubMed] [Google Scholar]
- Miller E. J. Isolation and characterization of a collagen from chick cartilage containing three identical alpha chains. Biochemistry. 1971 Apr 27;10(9):1652–1659. doi: 10.1021/bi00785a024. [DOI] [PubMed] [Google Scholar]
- Nicholson R. I., Golder M. P., Davies P., Griffiths K. Effects of oestradiol - 17beta and tamoxifen on total and accessible cytoplasmic oestradiol - 17beta receptors in DMBA-induced rat mammary tumours. Eur J Cancer. 1976 Sep;12(9):711–717. doi: 10.1016/0014-2964(76)90021-9. [DOI] [PubMed] [Google Scholar]
- Paavonen T., Andersson L. C., Adlercreutz H. Sex hormone regulation of in vitro immune response. Estradiol enhances human B cell maturation via inhibition of suppressor T cells in pokeweed mitogen-stimulated cultures. J Exp Med. 1981 Dec 1;154(6):1935–1945. doi: 10.1084/jem.154.6.1935. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schoen R. T., Greene M. I., Trentham D. E. Antigen-specific suppression of type II collagen-induced arthritis by collagen-coupled spleen cells. J Immunol. 1982 Feb;128(2):717–719. [PubMed] [Google Scholar]
- Scollay R., Jacobs S., Jerabek L., Butcher E., Weissman I. T cell maturation: thymocyte and thymus migrant subpopulations defined with monoclonal antibodies to MHC region antigens. J Immunol. 1980 Jun;124(6):2845–2853. [PubMed] [Google Scholar]
- Sloboda A. E., Birnbaum J. E., Oronsky A. L., Kerwar S. S. Studies on type II collagen-induced polyarthritis in rats. Effect of antiinflammatory and antirheumatic agents. Arthritis Rheum. 1981 Apr;24(4):616–624. doi: 10.1002/art.1780240408. [DOI] [PubMed] [Google Scholar]
- Sobhon P., Jirasattham C. Effect of sex hormones on the thymus and lymphoid tissue of ovariectomized rats. Acta Anat (Basel) 1974;89(2):211–225. doi: 10.1159/000144285. [DOI] [PubMed] [Google Scholar]
- Staines N. A., Hardingham T., Smith M., Henderson B. Collagen-induced arthritis in the rat: modification of immune and arthritic responses by free collagen and immune anti-collagen antiserum. Immunology. 1981 Dec;44(4):737–744. [PMC free article] [PubMed] [Google Scholar]
- Stimson W. H., Crilly P. J. Effects of steroids on the secretion of immunoregulatory factors by thymic epithelial cell cultures. Immunology. 1981 Oct;44(2):401–407. [PMC free article] [PubMed] [Google Scholar]
- Stuart J. M., Cremer M. A., Kang A. H., Townes A. S. Collagen-induced arthritis in rats. Evaluation of early immunologic events. Arthritis Rheum. 1979 Dec;22(12):1344–1351. doi: 10.1002/art.1780221205. [DOI] [PubMed] [Google Scholar]
- Sullivan D. A., Wira C. R. Hormonal regulation of immunoglobulins in the rat uterus: uterine response to a single estradiol treatment. Endocrinology. 1983 Jan;112(1):260–268. doi: 10.1210/endo-112-1-260. [DOI] [PubMed] [Google Scholar]
- Trentham D. E., Dynesius R. A., Rocklin R. E., David J. R. Cellular sensitivity to collagen in rheumatoid arthritis. N Engl J Med. 1978 Aug 17;299(7):327–332. doi: 10.1056/NEJM197808172990703. [DOI] [PubMed] [Google Scholar]
- Trentham D. E., Townes A. S., Kang A. H., David J. R. Humoral and cellular sensitivity to collagen in type II collagen-induced arthritis in rats. J Clin Invest. 1978 Jan;61(1):89–96. doi: 10.1172/JCI108929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ward H. W. Anti-oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels. Br Med J. 1973 Jan 6;1(5844):13–14. doi: 10.1136/bmj.1.5844.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weetman A. P., McGregor A. M., Smith B. R., Hall R. Sex hormones enhance immunoglobulin synthesis by human peripheral blood lymphocytes. Immunol Lett. 1981 Dec;3(6):343–346. doi: 10.1016/0165-2478(81)90064-x. [DOI] [PubMed] [Google Scholar]
