Influence of oral contraceptives on monocytes activity (with implications on modulation of the immune response)

Purpose: Monocytes are effector cells of the non-specific immune response involved in
the first recognition and response to pathogens. Sex hormones may play an important
role in regulating the immune responses and monocytes possess functional sex hormone
receptors. Therefore, the aim of this study was to evaluate whether the use of oral
contraceptives (OCs) can affect monocyte activity. To this end, we evaluate the effect of
OCs on pro-inflammatory and anti-inflammatory cytokines release by human monocytes
in response to known agonists of TLR4 and TLR2 receptors.
Methods: Primary human peripheral blood monocytes from healthy adult women treated
(FOCs) or non-treated (Fs) with OCs were isolated during the follicular phase of
their menstrual cycle and stimulated with either LPS or Pam2CSK4, in vitro. Release of
TNF-α, IL-6, IL-10 and IL-8 was investigated at specific hours post-stimulation, by Enzyme
Linked Immuno Sorbent Assay (ELISA).
Results: Our data showed that both agonists used induced the release of TNF-α, IL-6
and IL-8 by Fs and FCOs monocytes, whereas IL-10 was only induced by LPS in both
monocytes population, at 18 h. Differences in the kinetics of LPS-induced TNF-α were
observed in FOCs monocytes, in comparison with Fs, but not quite significant. Of interest,
a highly significant reduction of IL-8 detection, both in the basal condition and
after the two stimulations, and of IL-10, after stimulation with LPS only, was observed in
monocytes FCOs in comparison with Fs monocytes.
Discussion: Our results indicate that the FCOs monocyte response to LPS and
Pam2CSK4 is delayed (TNF-α and IL-10) or less intense (IL-8 and IL-10). These changes
might reduce monocyte ability to activate neutrophils and endothelial cells, to recruit
neutrophils and other granulocytes in the site of infection, and to suppress inflammation
and macrophage activity.
Conclusions: The use of COs might influence the immunomodulatory activity of monocytes
during infectious processes.
This work was supported by grant CPR.59632, LR72012MATTANA from the Regione
Sardegna.