An in vitro investigation of the anti-inflammatory and immunosuppressive effects of the synthetic contraceptives medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A)
Date
2005-03
Authors
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Publisher
Stellenbosch : University of Stellenbosch
Abstract
The aim of this study was to investigate the anti-inflammatory and
immunosuppressive effects of the synthetic progestins, MPA and NET-A on human
cells in vitro. These injectable contraceptives are used extensively throughout the
world, including Africa. The potential of these two synthetic hormones to have
certain immunosuppressive and GC properties have previously been shown.
Therefore, it was of concern to us to investigate whether these two hormones could
possibly demonstrate any of these GC-like properties at contraceptive doses. This
was achieved by determining the effects of these two synthetic hormones in vitro on
certain immunologic parameters.
Chapter 1 is a literature review on MPA, NET and GCs. This chapter starts with a
short introduction that sets the scene. The mode of action, effectiveness, sideeffects
as well as previously reported relevant data on both MPA and NET-A is
portrayed in this review. Research on the known GC, Dex, is also included in the
section dealing with GCs, because this synthetic hormone was used as a
comparative GC in all our experiments. This chapter soon makes the reader realize
how much evidence exists that indicate the possible immunosuppressive effects
these two contraceptive hormones, in particular MPA, could have.
The possible anti-inflammatory or pro-inflammatory effects of MPA and NET-A are
investigated in Chapter 2. This was done in vitro by measuring the effects of these
two synthetic hormones on the inflammatory markers, IL-6 and TNFα, by means of ELISA. In this chapter we demonstrate that MPA, even at contraceptive doses,
exhibits significant anti-inflammatory properties on both cytokines tested, while NETA
displayed considerably less anti-inflammatory tendencies. In its true antiinflammatory
manner, we found that Dex significantly inhibited the release of both
inflammatory markers from human monocytes.
In Chapter 3, we investigated the effects of MPA and NET-A on the activation of
human lymphocytes. This was achieved by flow cytometric measurement of the
expression of the activation membrane marker CD69 by CD4 and CD8 T cells. Here
we discovered that MPA had a very significant inhibitory effect on the activation of
both CD4+ and CD8+ T cells, while NET-A only significantly inhibited the activation of
CD8+ T cells. In addition, we found that the inhibition of CD4+ and CD8+ T cell
activation by MPA was more or less the same as the known GC, Dex, and in some
cases even more potent.
Chapter 4 consists of an investigation of the effects of MPA and NET-A on the
cytokines belonging to TH1 and TH2 subsets of CD4 T cells. This was achieved by
determining whether MPA and/or NET-A targeted specific subsets of T helper cells
by measuring the distinct regulatory cytokines, IFNγ and IL-4. The mechanism and
role of the T helper subsets are discussed in the introduction of this chapter. Our
results were portrayed as a ratio of TH2: TH1 on which the statistical analysis was
done. In addition to the analysis done on the ratio, we analyzed the helper subsets
separately in order to determine which subset(s) were influenced. The results of this chapter showed that neither MPA nor NET-A significantly affected either one of the
helper subsets, while Dex significantly decreased this ratio.
After our observed effects of MPA and NET-A on CD8 T cells, it became of interest
in Chapter 5 to investigate the effects of these two synthetic hormones on the CD8 T
cell-specific chemokine, RANTES. This was achieved by measuring the effects
MPA and NET-A had on RANTES production in vitro by means of ELISA.
Surprisingly, we discovered in this chapter that MPA and NET-A enhanced RANTES
production before and after activation of CD8 T cells. We also found that Dex had
the same effect on RANTES production, but to a lesser degree.
Finally, a general conclusion depicting the significance and implications of our
results as well as possible future research that is required is presented in Chapter 6.
It was of great importance to discuss and interpret the magnitude of data generated
out of all our experiments to the utmost of our capabilities. We found that MPA,
even at contraceptive doses, displayed significant immunosuppressive as well as
anti-inflammatory properties. NET-A, on the other hand, demonstrated weaker
immunosuppressive properties in our research and no significant anti-inflammatory
properties. These findings could have clinical implications in females being treated
with these synthetic contraceptives. We also demonstrated significant variation
found amongst genders in response to MPA, NET-A and Dex.
Description
Thesis (MScMedSc (Pathology. Medical Microbiology))--University of Stellenbosch, 2005.
Keywords
Medroxyprogesterone, Norethindrone, Anti-inflammatory agents, Immunosuppressive agents, Contraceptives, Dissertations -- Medicine, Theses -- Medicine, Dissertations -- Medical microbiology, Theses -- Medical microbiology