Kinetics of changes of LTE4 throughout the course of illness
LTE4 by itself has shown to cause endothelial dysfunction leading to
vascular leakage(16) . Since our results showed that urinary LTE4 levels
were significantly higher in patients with DHF, during early illness, we
sought to investigate if LTE4 levels were highest during the febrile
phase or the critical phase to further understand the possible
contribution of LTE4 to disease pathogenesis. In order to study the
kinetics of LTE4, we measured the urinary LTE4 levels in 25 patients
with DF and 23 patients who developed DHF throughout the course of
illness with urine samples taken at 9am in the morning. We found that
the urinary LTE4 levels rose in patients with DHF from day 3 to 5 and
remained high whereas there was no such rise from day 3 in patients with
DF (Fig 4a ). The patients who developed vascular leak (those
who developed DHF),entered the critical phase between day 4 and 5 of
illness and the rise of LTE4 levels in these patients was when they
entered the critical phase. Although the urinary LTE4 levels was high
throughout the illness in patients with DHF compared to those with DF,
this was not significant at any time point, probably due to the lower
number of patients included in the serial sampling, which was likely not
sufficiently powered to see changes of statistical significance.
We previously showed that levels of PAF showed a diurnal variation in
two cohorts of patients with acute dengue(9, 13). Patients with DHF, had
high PAF levels in the morning, which markedly reduced in the
afternoon2. Therefore, in order to find out if similar
changes were observed with LTE4, levels were measured in the morning
(9am) and late afternoon (3pm), in 14 patients with DF and 8 patients
with DHF. We found that in some patients while LTE4 levels fell towards
the afternoon, in others the LTE4 levels were higher at 3pm (Fig
4b) . Such differences in urinary LTE4 levels were seen in both patients
with DF and DHF (Fig 4b). Urinary LTE4 levels were higher in
the afternoon samples in 71% (10/14) patients with DF and 50% (4/8)
patients with DHF, when compared to the morning urinary LTE4 levels, but
overall the timing differences were not significant.
In some patients, several fold changes in the viral loads were also seen
between morning and afternoon samples in patients with both DF and DHF(Fig 4c) . Viral loads were higher in the afternoon samples in
38% (5/13) patients with DF and 57% (4/7) patients with DHF, when
compared to the morning viral loads. However, these changes in viral
loads did not reflect in the changes in urinary LTE4 levels. For
instance, while the LTE4 level increased the afternoon samples in 14
patients, the viral loads only increased in 9 samples (Fig
4c ).