Approach to the study of the role of sex hormones in autoimmunity

Steinberg, Alfred D.; Melez, Kathleen A.; Raveché, Elizabeth; Reeves, J P; Boegel, William A.; Smathers, P A; Taurog, Joel D.; Weinlein, Lisa; Duvic, Madeleine

doi:10.1002/art.1780221103

Cited by 180 publications

(73 citation statements)

References 12 publications

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“…1 nM in females, it is suggested that testosterone may suppress immunoglobulin production also in vivo under normal conditions. On the other hand, oestrogen has been shown to augment humoral immune responses [1,7,11,12,33], and we also found that this hormone increased spontaneous immunoglobulin production by human PBMC in vitro at physiological concentrations (paper submitted). Collectively, these data suggest that human humoral immune responses may be controlled by the balance of these sex hormone levels.…”

Section: Discussionmentioning

confidence: 51%

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Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells

Kanda

Tsuchida

Tamaki

1996

Clinical and Experimental Immunology

190

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SUMMARYWe studied the in vitro effect of testosterone on spontaneous immunoglobulin production by human peripheral blood mononuclear cells (PBMC). Testosterone inhibited IgG and IgM production by PBMC both from males and females. The inhibitory effect of testosterone was revealed at doses more than 1 nM, increased dose-dependently, and reached a plateau at 100 nM. At doses < 1000 nM, testosterone did not reduce cell viability. Testosterone treatment reduced IgG production by 59 . 0% and that of IgM by 61 . 3% compared with control. Immunoglobulin production by B cells was also suppressed by testosterone, though the magnitude of the suppressive effect on B cells was lower than that on whole PBMC; testosterone-induced decrease of IgG production compared with control was 26 . 9% and that of IgM was 24 . 9%. Exogenous IL-6 partially restored the impaired immunoglobulin production of testosterone-treated PBMC; IgG production in testosterone culture was increased by IL-6 from 35 . 6% to 66 . 5% of control and that of IgM was also increased from 38 . 9% to 71 . 2%, respectively. Testosterone treatment reduced IL-6 production of monocytes by 78 . 4% compared with control, but neither affected that of T cells or B cells. These results suggest that testosterone may suppress immunoglobulin production of human PBMC directly by inhibiting B cell activity and indirectly by reducing IL-6 production of monocytes. It is thus indicated that this hormone may have protective and therapeutic effects on human autoimmune diseases.

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Section: Discussionmentioning

confidence: 51%

“…Various studies have reported that testosterone suppresses humoral immune responses [1][2][3][4][5][6][7][8][9][10]. It is thus hypothesized that this hormone may have prophylactic and therapeutic effects on autoimmune diseases such as systemic lupus erythematosus (SLE) [1,2].…”

Section: Introductionmentioning

confidence: 99%

Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells

Kanda

Tsuchida

Tamaki

1996

Clinical and Experimental Immunology

190

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“…Sex steroids affect the maturation of organ systems, including the immune system (47), and are thought to play a role in autoimmune disorders. Feminizing steroids are known to exacerbate SLE by stimulating the immune response (48,49). Estrogen has been associated with decreased levels of T cells and natural killer cells, and increased levels of B cells (47,50).…”

Section: Discussionmentioning

confidence: 99%

Increased prevalence of renal disease in systemic lupus erythematosus families with affected male relatives

Stein

Olson

Gray‐McGuire

et al. 2002

Arthritis & Rheumatism

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Objective. To distinguish familial differences from sex-related differences in the clinical manifestations of systemic lupus erythematosus (SLE).Methods. A total of 372 affected individuals from 160 multiplex SLE pedigrees were analyzed. Twenty-five of these pedigrees contained at least 1 affected male relative. Comparisons of the presence of each of the 11 1982 American College of Rheumatology criteria for SLE were made between female family members with affected male relatives and those without affected male relatives, using Fisher's exact tests.Results. The presence of renal disease was significantly increased in female family members with an affected male relative when compared with those with no affected male relative (68% and 43%, respectively; P ‫؍‬ 0.002). This trend remained after stratifying by race and was most pronounced in European Americans. A familial basis for differences in hematologic and immunologic manifestations was also suggested, while arthritis and dermatologic features appeared to be most influenced by sex.Conclusion. Our results demonstrate that the increased prevalence of renal disease previously reported in men with SLE is, in large part, a familial rather than sex-based difference, at least in multiplex SLE families. Distinguishing familial from sex-related differences may facilitate efforts to understand the genetic and hormonal factors that underlie this complex autoimmune disease.

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“…Of particular interest in this context is further investigation of the reason for the strict male prevalence of the disease, seen after immunization of mice with homologous collagen, that is unusual in experimental as well as in human autoimmune disease (compare ref. 10).…”

Section: Discussionmentioning

confidence: 99%

Homologous type II collagen induces chronic and progressive arthritis in mice

Holmdahl

Jansson

Larsson

et al. 1986

Arthritis & Rheumatism

179

110

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Native mouse type I1 collagen was used for immunization of DBA/l mice. Arthritis developed exclusively in male animals and was characterized by a variable and delayed onset, a slow and progressive devebpment, and frequent exacerbations of disease in several joints including those that were previously affected. Titers of anti-type I1 collagen autoantibodies were found not to correlate well with arthritis development. It appears that experimental arthritis induced with homologous type I1 collagen resembles rheumatoid arthritis in humans, both in certain clinical features and in the lack of correspondence between anti-type I1 collagen autoantibody titers and disease symptoms.Type I1 collagen-induced arthritis provides an experimental model for autoimmune polyarthritis , originally introduced by Trentham et a1 in rats (1) and by Courtenay et a1 in mice (2). In rats, both homologous and heterologous type 11 collagen have been used for induction of arthritis (l), but in mice, only heterologous lype I1 collagen has been used (2). In both rats and mice, the disease course is characterized by a severe, acute phase, with no later exacerbations of disease (3). High titers of antibody against heterologous type 11 collagen have been seen preferentially in arthritic animals, suggesting that levels of anti-type I1 collagen antibodies may be critical for the development of the disease (4). Also, the successful induction of arthritis with immunoglobulin fractions from diseased animals has provided arguments for an important and perhaps necessary role of anti-type I1 collagen antibodies in collagen arthritis (5).The relevance of type I1 collagen-induced arthritis in rodents as a model for human rheumatoid arthritis has been a matter of debate. Both the lack of a relapsing character in collagen-induced arthritis and the lack of circulating anti-type I1 collagen antibodies in most humans with rheumatoid arthritis have been used to emphasize the dissimilarities between the respective conditions (see ref.3). It is not certain, however, that immunization with heterologous collagens, the method that has thus far been used in animal studies, provides the best model for a hypothetical autoimmunization against collagen in humans. It is possible that immunization of animals with homologous collagen could be more useful in this respect.Therefore, in the present study, we investigated the arthritis that can be induced in DBAl1 mice after immunization with homologous collagen. We characterized a large group of immunized animals as to clinical course and mean antibody titers against the immunogen, and in addition, we analyzed the disease course, the development of anti-type I1 collagen autoantibodies, and the final histopathologic picture in 10 male and 9 female DBAI1 mice. It is demonstrated that arthritis induced with mouse collagen is progressive and proceeds with an intermittent course. It is

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Approach to the study of the role of sex hormones in autoimmunity

Cited by 180 publications

References 12 publications

Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells

Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells

Increased prevalence of renal disease in systemic lupus erythematosus families with affected male relatives

Homologous type II collagen induces chronic and progressive arthritis in mice

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