The effect of azithromycin on acute and chronic inflammation in an in vivo experimental model.
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Date
2013
Authors
Du Bois, A. H.
Editors
Advisors
Bartold, Mark
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Thesis
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Abstract
Background: Macrolide antibiotics have been found to have both antimicrobial and antiinflammatory
properties. They may be useful adjuncts in the treatment of conditions in which
both these factors play a role, such as periodontitis.
Objectives: The aim of this study was to evaluate the effect of azithromycin in a rat model
of experimentally induced acute and chronic inflammation.
Material and methods: Polyurethane sponges loaded with either heat killed Porphyromonas
gingivalis (HKPG), Mycobacterium tuberculosis (HKTB) or Phosphate Buffered Saline
(PBS) were surgically implanted into the fore flanks of rats. To determine any acute
inflammatory effects animals received azithromycin 4 days prior to surgery, while to
determine the effects on chronic inflammation animals did not receive azithromycin until day
25 post operatively. The control groups did not receive azithromycin. The sponges were
retrieved at days 7, 14, 21, 35 and 49, wet weights recorded and then processed for
histological evaluation of acute and chronic inflammation and fibrosis. Additionally,
immunohistochemical staining was used to identify macrophages using CD163 and CD68
macrophage markers at days 21 and 35. Biochemical analyses were used to determine serum
levels of C-reactive protein (CRP) and hydroxyproline (HP) content in the retrieved sponges.
Results: No differences were found between wet and dry weights of sponges for any of the
groups.
Acute Inflammation: A trend for lower inflammation and infiltration scores was observed
for all azithromycin treated groups compared to untreated groups, although this was not
statistically significant. Azithromycin reduced neutrophil infiltration in all groups, but this
reduction was only significant in the acute HKTB group (p= 0.008). Although azithromycin
reduced CD68 cell counts between treated and untreated animals in all groups, this was found
to be significant only for animals with PBS sponges at day 21 as well as day 35 and TB
sponges at day 35. Similarly, for CD163 it was found that although azithromycin reduced
counts of CD163 positive cells, this was only significant at day 35 for PBS (p<0.001) and
HKTB (p<0.001). The hydroxyproline content differed within sponges for rats with HKTB
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sponges at days 7 (p=0.001), 14 (p=0.04) and 21 (p=0.001) as well as PBS sponge implants
was at all time points (p<0.05) for animals that had received azithromycin, compared to
control animals.
CRP levels increased between 32-58% in all groups after sponge implantation, but a
significant difference was only observed between the azithromycin treated and untreated
groups at day 21 for animals with PBS sponge implants.
Chronic Inflammation: Animals in this part of the study received the late (day 25)
administration of azithromycin. No statistically significant effects were demonstrated on any
of the measured (histological or biochemical) parameters, except the sponge hydroxyproline
content, which was significantly reduced at day 35 for animals that had received HKTB
(p=0.012) and HKPG (p=0.025) sponges.
Conclusions: Azithromycin has the potential to suppress neutrophil infiltration and thus
modulate acute inflammation in a subcutaneous rat model for inflammation. The drug has a
limited effect on macrophage infiltration and the collagen content of the resulting scar tissue,
but no significant impact on serum CRP levels. Once chronic inflammation has ensued, the
anti-inflammatory effect of azithromycin was less marked than effects on acute inflammation,
although a tendency for reduction of inflammation was observed.
School/Discipline
School of Dentistry
Dissertation Note
Thesis (D.Clin.Dent) -- University of Adelaide, School of Dentistry, 2013
Provenance
Copyright material removed from digital thesis. See print copy in University of Adelaide Library for full text.