Vol 44 # 4 December 2012 - Kma.org.kw

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Asthma during Pregnancy: An Immunologic Perspective
December 2012
Interestingly, immune mechanisms involved in the
maintenance of asthma-related symptoms are regulated
by Th2-mediated mechanisms as in normal pregnancy
which leads us to propose that pregnancy may worsen
asthma by bringing about a stronger bias towards Th2
reactivity. However this rather simplistic notion is
complicated by the fact that the disease becomes worse
in only about a third of the patients and, not as one
might predict, in all the patients.
IMMUNE STATUS IN ASTHMATIC WOMEN WHO
BECOME PREGNANT
Pregnancy is proposed to be a state of wide-spread
lymphocyte activation, but at the same time it may
blunt lymphocyte activation which characterizes
bronchial asthma [81] . However, immunological
changes in asthmatic women during pregnancy are
not well elucidated. Tamasi et al [82] reported signs of
pregnancy-induced attenuation of allergic responses
in asthmatic pregnant women. Activated pools within
CD4 + and CD8 + T cells were larger, and the number
of natural killer T (NK-T) cells was increased both
in non-pregnant asthmatic and in healthy pregnant
subjects (compared to non-pregnant healthy controls),
but in well-controlled pregnant asthmatics no further
lymphocyte activation was observed, suggesting
that the immunosuppressive effect of uncomplicated
pregnancy may dull lymphocyte activation which
characterizes asthma. In addition, as a sign of an
enhanced T cell apoptosis, higher numbers of cytotoxic
T cells was detected in healthy pregnant women than in
healthy non-pregnant women, together with a positive
correlation between cytotoxic T cell counts and birth
weights in healthy but not in asthmatic pregnancies. On
the other hand, in another study on poorly-controlled
asthmatic pregnant women, a substantial number of
peripheral IFN-γ-producing cells were detected, and a
significant negative correlation was revealed between
the number of IFN-γ-positive T cells and birth weight
of newborns, suggesting that intrauterine growth
restriction can be related to active, asthma-associated
maternal immune reactions [82] .
Bohacs et al [81] reported an increased prevalence
of regulatory T (Treg) cells in peripheral blood of
healthy pregnant women but a lower prevalence of
Treg cells and an elevated prevalence of NK-T cells
in pregnant asthmatic women compared to healthy
pregnant women. They also reported lower effector /
mem¬ory ratios and higher naive T cell prevalence in
asthmatic pregnant patients compared to non-pregnant
asthmatics [83] .
Analysis of immune cells in the maternal circulation
indicates that circulating white cells are altered in
asthmatics when compared to non-asthmatics and that
these alterations may contribute to worsening asthma
during pregnancy. Maternal circulating monocyte
populations were significantly increased in pregnant
asthmatic women not using inhaled steroids for the
treatment of their disease [84] . Monocytes play important
inflammatory roles in asthma, as the precursors to
macrophages and also through their interaction with
Th2 lymphocytes, eosinophils and mast cells within
the lung. Murphy et al [84] examined placental Th2:Th1
cytokine mRNA ratios and found a significant increase
in placental Th2:Th1 cytokine mRNA ratios in females,
as assessed by measuring TNFα (Th1) and IL-5 (Th2)
mRNA.
A CYTOKINE LINK BETWEEN ASTHMA AND
PREGNANCY
As pregnancy is a Th2-type situation, it is tempting
to predict that symptoms in asthmatic women may
become worse when they get pregnant, because
asthma is also a Th2-type situation. It is a sort of
an “immunological double whammy”! One might
speculate that the Th2 predominance seen in pregnancy
might worsen asthma situations; by corollary then,
all asthmatic women should have worsened asthma
symptoms when they become pregnant. However,
this is not the case; the dogma holds that only about
33% of asthmatic women have worsened symptoms
during pregnancy, while approximately 33% actually
get better!
There is a lack of studies on longitudinal assessment
of cytokine bias during and after pregnancy in
asthmatics that become pregnant as also possible effects
of changes in cytokine patterns on asthma symptoms
during pregnancy. Rastogi et al [85] reported a nonsignificant
trend towards decreased intracytoplasmic
levels of IFNγ and increased IL-4 levels in pregnant
asthmatics. Non-asthmatic pregnant women were not
studied. Interestingly, these researchers demonstrated
a decline in IP-10/eotaxin ratio over the course of
pregnancy; this ratio was also shown to be associated
with worse asthma symptoms. The levels of other
cytokines were not estimated in this study. Clearly this
aspect needs to be investigated further.
Tamasi et al [86] demonstrated increased levels of
IFNγ-producing T cells in pregnant asthmatics as
compared to non-pregnant asthmatics. IL-4-producing
T cells were also increased in number though to a much
lower extent, leading these researchers to conclude
that pregnancy in asthmatics leads to a dominant
IFNγ response. While these results are interesting, it
should be noted that pregnant non-asthmatics were
not compared, nor were other cytokines tested.
CONCLUSION
The jury is still out; as asthma is characterized
by increased Th2 polarization, we suggest that
pregnancy-associated Th2 polarization may contribute
mechanistically to worse birth outcomes. Our