Abstract
A group of 49 multiple myeloma patients, 20 men and 29 women, were evaluated. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-oestradiol (E) and testosterone (T) serum concentrations have been detected by radioimmunoassay. Peripheral blood lymphocyte proliferation in response to phytohaemagglutinin (PHA), concanavalin A (ConA), recombinant interleukin-2 (rIL-2) and dextran sulphate (DxS) was investigated. Our findings provide evidence for two different patterns of sex hormone changes and immune dysfunctions presented differently by male and female multiple myeloma patients. In men increased FSH, LH and E concentrations and an augmented E to T ratio were associated with decreased lymphocyte blastogenic response to PHA, ConA and increased proliferation to rIL-2 and DxS. Female patients with multiple myeloma demonstrated normal values of FSH, LH and T, but a diminished E level and decreased E to T ratio correlated with a lymphocyte normal response to PHA and ConA and augmented blastogenesis to IL-2 and DxS. Our data, while admittedly preliminary, suffice to provide an indication of sex hormone changes in multiple myeloma patients, which could be responsible, at least in part, for the immune dysfunction observed in multiple myeloma.
Key words: Multiple myeloma, Sex hormones, Immune dysregulation
References
- 1.Ablin RJ. Modulatory effects of estrogen on immunologic responsiveness. Am J Rep Immunol. 1981;1:206. doi: 10.1111/j.1600-0897.1981.tb00038.x. [DOI] [PubMed] [Google Scholar]
- 2.Ablin RJ. Immunomodulatory effects of oestrogen. J Immunol. 1984;132:3229. [Google Scholar]
- 3.Ablin RJ, Bruns GR, Guinan P, Bush IM. The effect of estrogen on the incorporation of3H-thymidine by PHA-stimulated human peripheral blood lymphocytes. J Immunol. 1974;113:705. [PubMed] [Google Scholar]
- 4.Belchetz P. Endocrinology of menopaus. Practitioner. 1990;234:491. [PubMed] [Google Scholar]
- 5.Bergmann L, Mitrou PS, Weber KC, Kelker W. Imbalances of T-cell subsets in monoclonal gammopathies. Cancer Immunol Immunother. 1984;17:112. doi: 10.1007/BF00200046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Berson SA, Yalow RS. Radioimmunoassay of ACTH in plasma. J Clin Invest. 1968;47:2725. doi: 10.1172/JCI105955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Casper RF, Yen SSC, Wilkes MM. Menopausal flushes: a neuroendocrine link with pulsatile luteinizing hormone secretion. Science. 1979;205:823. doi: 10.1126/science.462193. [DOI] [PubMed] [Google Scholar]
- 8.Cohn DA. High sensitivity to androgen as a contributing factor in sex differences in the immune response. Arthritis Rheum. 1979;22:1218. doi: 10.1002/art.1780221109. [DOI] [PubMed] [Google Scholar]
- 9.Commer T, Klein B, Jourdan M, Bataille R. Production of interleukin 2 in multiple myeloma. Clin Exp Immunol. 1986;63:533. [PMC free article] [PubMed] [Google Scholar]
- 10.Committee of the Chronic Leukemia-Myeloma Task Force Proposed guidelines for protocol studies. Plasma cell myeloma. Cancer Chemother Rep. 1973;4:145. [Google Scholar]
- 11.Elves MW, Roath S, Israelis MC. The response of lymphocytes to antigen challenge in vitro. Lancet. 1963;1:806. [Google Scholar]
- 12.Frey-Wettstein S, Craddock CA. Testosterone induced depletion of thymus and marrow lymphocytosis as related to lymphopoiesis and hematopoiesis. Blood. 1979;35:257. [PubMed] [Google Scholar]
- 13.Fuji H, Nawa Y, Tsuchiya H, Matsuno K, Fukumoto T, Fukuda S, Kotani M. Effect of a single administration of testosterone on the immune response and lymphoid tissues in mice. Cell Immunol. 1975;20:315. doi: 10.1016/0008-8749(75)90108-2. [DOI] [PubMed] [Google Scholar]
- 14.Giovarelli M, Foa R, Benetton G, Fierro MT, Forni G. Release of interleukin-2 like material by B-chronic lymphocytic leukemia cells. An autocrine or paracrine model of production and utilization. Leukemia Res. 1988;12:201. doi: 10.1016/0145-2126(88)90137-3. [DOI] [PubMed] [Google Scholar]
- 15.Graff RJ, Lappe MA, Snell GD. The influence of the gonads and adrenal glands on the immune response to skin grafts. Transplantation. 1969;7:105. doi: 10.1097/00007890-196902000-00003. [DOI] [PubMed] [Google Scholar]
- 16.Gross HA, Ruder HJ, Brown K, Lipsett MB. A radioimmunoassay for plasma corticosterone. Steroids. 1972;20:681. doi: 10.1016/0039-128x(72)90051-7. [DOI] [PubMed] [Google Scholar]
- 17.Grossman CJ. Regulation of the immune system by sex steroids. Endocrinol Rev. 1984;5:435. doi: 10.1210/edrv-5-3-435. [DOI] [PubMed] [Google Scholar]
- 18.Grossman CJ. Interactions between the gonadal steroids and the immune system. Science. 1985;227:257–261. doi: 10.1126/science.3871252. [DOI] [PubMed] [Google Scholar]
- 19.Hitton JD, Jacobs HS, James VHT. Steroid endocrinology after the menopause: a review. J R Soc Med. 1979;72:835. doi: 10.1177/014107687907201109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Juliusson G. Leukemic B-lymphocytic malignancy. A clinical, immunological and cytogenetic study, utilizing mitogens to activate and differentiate malignant B-lymphocytes in vitro. Stockholm, Sweden: Dissertation, Karolinska Institute; 1985. p. 11. [Google Scholar]
- 21.Juliusson G, Robèrt KH, Nilsson B, Hahrton G. Prognostic value of B-cell mitogen-induced and spontaneous thymidine uptake in vitro in chronic B-lymphocytic leukaemia cells. Br J Haematol. 1985;60:429. doi: 10.1111/j.1365-2141.1985.tb07440.x. [DOI] [PubMed] [Google Scholar]
- 22.Lahat N, Aghaie E, Quitt M, Froom P. Autologous mixed lymphocyte reaction in multiple myeloma patients: effect of adherent mononuclear cells and T lymphocytes. Diagn Immunol. 1986;40:75. [PubMed] [Google Scholar]
- 23.Lantz O, Grillot-Courvalin C, Schmitt C, Fermand JP, Broet JC. Interleukin 2 induced proliferation of leukemic human B cells. J Exp Med. 1985;161:1225. doi: 10.1084/jem.161.5.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Lauria F, Foa R, Cavo M, Gobbi M, Raspadori D, Giubellino MC, Tazzari PL, Tura S. Membrane phenotype and functional behaviour of T lymphocytes in multiple myeloma: correlation with clinical stages of the disease. Clin Exp Immunol. 1984;56:653. [PMC free article] [PubMed] [Google Scholar]
- 25.Luster MI, Hayes HT, Korach K, Tucker AN, Dean JH, Greenlee WF, Boorman GA. Estrogen immunosuppression is regulated through estrogenic responses in the thymus. J Immunol. 1984;133:111. [PubMed] [Google Scholar]
- 26.Mac Kenzie MR, Paglieroni T. Multiple myeloma: an immunologic profile: I Peripheral blood studies. J Immunol. 1977;118:1864. [PubMed] [Google Scholar]
- 27.Panayotides P, Porwit A, Lenkei R, Reizenstein P. Interleukin-2 can induce proliferation of leukemic B-cells in prolymphocytic leukemia. Eur J Hematol. 1987;38:274. doi: 10.1111/j.1600-0609.1987.tb01176.x. [DOI] [PubMed] [Google Scholar]
- 28.Petersen J, Drivsholm A, Brandt M, Ambjornsen A, Dickmeiss E. B-lymphocyte function in multiple myeloma: analysis of T cell- and monocyte-dependent antibody production. Eur J Hematol. 1989;42:193. doi: 10.1111/j.1600-0609.1989.tb01210.x. [DOI] [PubMed] [Google Scholar]
- 29.Preud'homme JL, Klein M, Labaume S, Seligmann M. Idiotype-bearing and antigen-binding receptors produced by blood T lymphocytes in a case of human myeloma. Eur J Immunol. 1977;7:840. doi: 10.1002/eji.1830071204. [DOI] [PubMed] [Google Scholar]
- 30.Robèrt KH, Juliusson G, Biberfeld P. Chronic lymphocytic leukemia cells activated in vitro reveal changes that characterize B-prolymphocytic leukaemia and immunocytoma. Scand J Immunol. 1983;17:397. doi: 10.1111/j.1365-3083.1983.tb00805.x. [DOI] [PubMed] [Google Scholar]
- 31.Rossi JF, Klein B, Commes T, Jourdan M. Interleukin 2 production in B cell chronic lymphocytic leukemia. Blood. 1985;66:840. [PubMed] [Google Scholar]
- 32.Rosemberg E. Immunoreactivity of standards and reference preparations used in the radioimmunoassay of follicle stimulating and luteinizing hormones in serum. J Clin Endocrinol. 1979;48:163. doi: 10.1210/jcem-48-1-163. [DOI] [PubMed] [Google Scholar]
- 33.Rouabhia M, Deschaux PA, Othmane O. Contribution a l'étude de la neuroimmunomodulation de la réponse immunitaire par le système endocrinien: effet de l'hormone luteinisante (LH) sur la réponse proliferative des lymphocytes. Jpn J Med Sci Biol. 1987;40:147. [PubMed] [Google Scholar]
- 34.Spira G, Carter A, Tatarsky I, Silvian I. Lymphocyte subpopulations in benign monoclonal gammopathy. Scand J Haematol. 1983;31:78. doi: 10.1111/j.1600-0609.1983.tb02140.x. [DOI] [PubMed] [Google Scholar]
- 35.Talal N, Roubinian JR. Sex hormones and autoimmunity. In: Rose NR, Bigazzi PE, Warner NL, editors. Genetic control of autoimmunity. New York: Elsevier/North Holland; 1978. p. 163. [Google Scholar]
- 36.Thompson JS, Crawford MK, Reilly RW, Severson CD. The effect of estrogenic hormones on immune responses in normal and irradiated mice. J Immunol. 1967;98:331. [PubMed] [Google Scholar]
- 37.Tsatsoulis A, Shalet SM, Robertsow WR. Bioactive gonadotrophin secretion in man. Clin Endocrinol. 1991;35:193. doi: 10.1111/j.1365-2265.1991.tb03522.x. [DOI] [PubMed] [Google Scholar]
- 38.Waldman TA, Goldman CK, Robb RJ, Depper JM, Warren JL, Sharrow SO, Bongiovanni KE, Korsmeyer SJ, Green WC. Expression of interleukin 2 receptors on activated human B cells. J Exp Med. 1984;160:1450. doi: 10.1084/jem.160.5.1450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Wyle FA, Kent JR. Immunosuppression by sex steroid hormones. Clin Exp Immunol. 1977;27:407. [PMC free article] [PubMed] [Google Scholar]