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EVALUATION OF SERUM INFLAMMATORY CYTOKINES IN CATS WITH

ORAL DISEASE BEFORE AND AFTER TREATMENT


WATANABE R1, AUGER JP2, SEGURA M2, STEAGALL P1
1Département
de sciences cliniques, Faculté de médecine vétérinaire, Université de Montréal, Canada
2Département de pathologie et microbiologie, Faculté de médecine vétérinaire, Université de Montréal, Canada

INTRODUCTION RESULTS
l Periodontal disease (PD) is a common disease which produces pain and l Results are shown in Figure 4.
inflammation in cats.1
l IL-8 was significantly decreased on day 6 when compared with day 0 in cats
l Periodontal inflammation increases salivary and serum concentrations of with minimal oral disease (p = 0.003).
immunoglobulins.2,3 Inflammatory cytokines are upregulated in local dental
l IFN-γ, ΙL-4, IL-6, IL-8, MCP-1, RANTES, and SCF were significantly decreased
lesions in cats.4,5 However, it is unclear if serum concentrations of these
on day 6 when compared with day 0 in cats with severe oral disease (p =
cytokines are also elevated in PD.
0.008, 0.0004, 0.0006, 0.006, 0.007, 0.003 and 0.0003, respectively).
l This study aimed to evaluate serum inflammatory cytokines in cats with
l SCF was significantly higher in cats with severe disease than those with
minimal or severe PD before and after treatment.
minimal disease on day 0 (p = 0.006).
l The hypotheses were: 1) some inflammatory cytokines would be increased in
l IL-12p40 was significantly increased on day 6 when compared with day 0 in
cats with severe PD compared with those with minimal PD; 2) treatment of
both minimal and severe groups (p = 0.005 and 0.0002, respectively).
oral disease would modulate the concentration of inflammatory cytokines
and 3) some inflammatory cytokines would be associated with dental l There were positive associations between sFAS, IL-6, SDF-1, and MCP-1, and
parameters. the number of teeth resorption (p = 0.048, 0.028, 0.012, and 0.047,
respectively), between sFAS and the number of missing teeth (p = 0.02),
between KC and the number of teeth fracture (p = 0.038), and a negative
MATERIALS & METHODS association between sFAS and TNF-α and the number of teeth fracture (p =
0.03 and 0.011, respectively).
l Ethics committee: 17- Rech-1890 Figure 4 – Serum concentration of inflammatory cytokines in cats with
l Study design: Prospective, blinded clinical trial minimal or severe dental disease before (day 0) and after treatment (day 6)
Serum concentraIon of inflammatory cytokines
Serum concentraIon of inflammatory cytokines
l Animals: Twenty-four cats (6 3 years old; 4.9 1.7 kg) from local shelters Serum concentraIon of inflammatory cytokines
*
were divided into two groups based on disease severity (Figure 1). 1000
1000
l Treatment of oral disease: Cats were admitted on day 0. They underwent 1000 *
* *
general anesthesia (acepromazine, hydromorphone, propofol, isoflurane,
*
meloxicam, and dental nerve blocks) on day 1 for treatment of oral disease. *
Serum concentraIon (pg/mL)

*
Serum concentraIon (pg/mL)

Cats were discharged on day 6; meloxicam was administered up to day 4


Serum concentraIon (pg/mL)

*
(Figure 2).
100
100
l Blood sampling: Whole blood was collected on day 0 and 6 and allowed to 100
*
clot at room temperature for 40 to 60 min (Figure 2).6 Clotted samples were * *
centrifuged
26
at 3000 rpm for 10 min, and serum was removed, aliquoted, and
Atlas of Normal Radiographic Anatomy and Anatomic Variants in the Dog and Cat

stored in cryovials at −80 ℃ until use.


Upper jaw Incisors

l Cytokine analysis: Samples were analyzed for concentrations of 19 analytes 103


102
101 201
202
203
10
using commercially available feline-specific multiplex cytokine kits. a The plate 10
Right upper Left upper
permanent permanent Canine 104 204
1 2 10
was analyzed using the Luminex MAGPIX platformb and softwarec (Figure 3).
Right upper Left upper
105 205
106 206

Analytes with concentrations more than 50% out of the range of analysis
Right upper
deciduous
Left upper
deciduous
Premolars
107 207

were excluded from the analyses.


5 6 108 208

109 209

l Statistical analysis: Cytokine concentrations were compared after log10 Molars


110 210

1
transformation to normalize distributions between day 0 and 6 and between
Right Left
411 311 1
sFAS

FLT-3L

IL-2

IL-4

IL-6

IL-8
IFN-γ

IL-1β

IL-12P40

IL-13

IL-18

PDGF-BB

RANTES

SCF

SDF-1
KC

MCP-1

TNF-α
sFAS

FLT-3L

IL-2IL-2

IL-4IL-4

IL-6IL-6

IL-8IL-8
IFN-γ

IL-1β

IL-12P40

IL-13

IL-18

PDGF-BB

RANTES

SCFSCF

SDF-1
KC KC

MCP-1

TNF-α
Molars 410 310

dental severity groups using a linear mixed model with Benjamini-Hochberg


Right lower Left lower 1
sFAS

FLT-3L

IFN-γ

IL-1β

IL-12P40

IL-13

IL-18

MCP-1

PDGF-BB

RANTES

SDF-1

TNF-α
permanent permanent 409 309
Right lower Left lower
4 3
sequential adjustment procedure (p < 0.05). Dental parameters were added 408 308
Analyte
Analyte
as a covariate to the model.
407 307
Premolars
406 306 Minimal disease day day
0 0 Minimal disease day day
6 6
Right lower
deciduous
Left lower
deciduous 405 305
The bars and error bars represent least squares means
AnalyteMinimal disease Minimal disease
8 7 Severe disease
Severe day day
disease 0 0 Severe disease
Severe day day
disease 6 6
and standard errors, respectively. Minimal disease day 0 Minimal disease day 6
Figure 1 – Dental scores based on number of dental extractions7
Canine 404 304

A Lower jaw
403
402
303
302
401 301
* Significantly different than baseline or disease group. Severe disease day 0 Severe disease day 6
B Incisors
Figure 1-a
Incisors
• If ≥ 7 incisive teeth
101 201
103
102 202
203 and/or first premolars
CONCLUSIONS
Canine 104 204
Right upper Left upper of the mandible were
extracted, they were
Premolars
106
3 206

counted as 2 points,
108
107
1 207

208 otherwise if ≤ 6 teeth l This study identified specific cytokines that are affected by oral disease and
2 were extracted, they surgical treatment. These concentrations may have been changed by the
109 209
were counted as 1 point.
Molar administration of meloxicam post-operatively.
Total score was
An overexpression of some cytokines could be involved in the pathogenesis
l

2 Figure 1-b
calculated. l
Molar 409 309
Cats were allocated to
l 2-7. The modified Triadan system of dental identification. In
Figure
of tooth resorption/fracture.
Premolars
408 1 308 the minimal (Figure 1-a)
A, each quadrant of the mouth is designated by a number; this is the
first digit in identification. With respect to permanent teeth, the right

3
407 307
or severe (Figure 1-b)
maxilla is designated 1, the left maxilla 2, the left mandible 3, and the
right mandible 4. When describing deciduous teeth, the right maxilla
Right lower Left lower
oral disease group if
ACKNOWLEDGMENTS
is designated 5, the left maxilla 6, the left mandible 7, and the right
Canine 404 304 mandible 8. B, Schematic model of a canine jaw with each permanent
403
402
303
302
dental scores were ≤ 7
tooth identified. The numbering always begins on midline; the central
incisor is designated 01, the canine 04, and the first molar 09.
C Incisors
401 301
or ≥ 8, respectively.
C, Schematic model of a feline jaw, showing tooth identification.

l This study was funded by Hill’s Pet Nutrition and a


Figure 2 – Timeline of the study Discovery Grant by the Natural Sciences and
Engineering Research Council of Canada (RGPIN-
Blood sampling Dental procedures Blood sampling
Scaling
2018-03831).
Meloxicam
Day 0
Tooth extrac;ons 0.05 mg/kg/PO
Day 6
l Guy Beauchamp PhD for the statistical analyses.
Admission Day 1 Day 2 - 4 Discharge

REFERENCES
Figure 3 – Feline-specific multiplex cytokine kitsa, Luminex MAGPIXb and softwarec
a b c 1. Southerden P. In Pract 2010; 32: 2–7.
2. Cave NJ et al. Vet Q. 2012; 32: 131-144.
3. Harley R et al. Vet Rec. 2003; 152: 125-129.
4. Booij-Vrieling HE et al. Vet Immunol Immunopathol. 2009; 132: 160-166.
5. Harley R et al. Clin Diagn Lab Immunol. 1999; 6: 471-478.
6. Gruen ME et al. Vet Immunol Immunopathol. 2017; 183: 49-59.
7. Thrill DE et al. The skull In: Atlas of normal radiographic anatomy & anatomic variants in the dog
a FCYTMAG-20K-PMX, b MAGPIX, and C xPONENT v.4.2, Luminex Corporation, TX, USA and cat 2nd ed. Missouri: ELSEVIER; 2016. P. 20-48.

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