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Medroxyprogesterone acetate enhances in vivo and in vitro antibody production
M Vermeulen1, P Pazos, C Lanari
1Laboratory of Immunology, IIHEMA, National Academy of Medicine, Buenos Aires, Argentina. mirtagiordano@imaginaria.com.ar
Abstract:
In the present study we examine the effects of medroxyprogesterone acetate (MPA) on the specific antibody secretion to T-dependent antigens. Our results show that the in vivo administration of MPA to mice, 7 or 90 days before immunization with sheep red blood cells (SRBC), significantly enhanced both, primary and secondary antibody responses, without affecting delayed-type hypersensitivity (DTH). These effects could be counteracted by the anti-progestin onapristone or ZK 98299 (ZK) suggesting that MPA interacted with progesterone (PRG) receptors to increase B-cell response. To better understand the mechanisms involved in MPA activity we carried out cultures of splenocytes, bone marrow cells or lymph node cells from immunized mice in the presence of MPA, and evaluated the amount of antibody release to supernatants. We found that low doses of MPA (10(-9) M and 10(-10) M) significantly enhanced the in vitro production of specific immunoglobulin G (IgG) antibodies, an effect that appears to involve the interaction of the progestin with PRG receptors, as judged by the inhibition of MPA effects with ZK (10(-8) M) or RU486 (10(-9) M). These receptors were detected by flow cytometry analysis in a proportion of T lymphocytes. Because MPA did not increase the number of immunoglobulin-secreting cells, our findings suggest that MPA enhanced the capacity of individual cells to produce specific immunoglobulin.
Insights
Medroxyprogesterone acetate (MPA) boosts specific antibody production in mice, enhancing immune responses to T-dependent antigens. This effect is mediated through progesterone receptors and increases individual cell antibody production capacity.
Area of Science:
- Immunology
- Endocrinology
Background:
- Medroxyprogesterone acetate (MPA) is a synthetic progestin.
- The impact of MPA on specific antibody secretion to T-dependent antigens requires further elucidation.
Purpose of the Study:
- To investigate the effects of MPA on specific antibody secretion to T-dependent antigens.
- To explore the mechanisms underlying MPA's influence on B-cell responses and antibody production.
Main Methods:
- In vivo administration of MPA to mice prior to immunization with sheep red blood cells (SRBC).
- Assessment of primary and secondary antibody responses and delayed-type hypersensitivity (DTH).
- In vitro cultures of splenocytes, bone marrow cells, and lymph node cells with MPA, and evaluation of antibody release.
- Flow cytometry analysis to detect progesterone receptors (PRG) on lymphocytes.
Main Results:
- In vivo MPA administration significantly enhanced both primary and secondary antibody responses to SRBC without affecting DTH.
- Low doses of MPA in vitro significantly enhanced specific immunoglobulin G (IgG) antibody production.
- MPA's effects were counteracted by anti-progestins (onapristone, ZK 98299, RU486), suggesting interaction with PRG receptors.
- Progesterone receptors were detected on a proportion of T lymphocytes.
Conclusions:
- MPA enhances specific antibody secretion to T-dependent antigens, likely via PRG receptor interaction.
- MPA increases the capacity of individual B-cells to produce specific immunoglobulins, rather than increasing the number of antibody-secreting cells.