In our study, an experimental model of Ag-induced arthritis (AIA) in mice was shown to mimic several aspects of the clinical-associated comorbidity periodontal disease (PD), through increased systemic reactivity to auto-Ags in a way dependent on oral microbiota. Moreover, it was shown that TNF-α might play an important role in AIA-induced PD, which was demonstrated by the use of an anti–TNF-α therapy with infliximab (the protocol was based on previous publications listed below).

Infliximab is a chimeric IgG1κ mAb, composed of human and murine regions, raised against TNF-α. Several studies demonstrate that infliximab may neutralize both human and murine TNF-α (118). There are many published studies in the literature supporting the effectiveness of using this Ab under different experimental conditions in murine models, including experimental colitis (1, 10), hypothalamic inflammation (2), allergic rhinitis (3), experimental Alzheimer’s disease (4), chronic hepatitis C (5), mucopolysaccharidoses (6), aneurysm (7), in vitro conditions by using macrophages (8),murine aortic transplant model (9), HSV-induced inflammation (11), Fas stimulation (12), acute asthma (13), aortic calcification during diabetes (14), and distinct mouse models of joint inflammation (1518). In several of these studies, the use of isotype controls did not mimic the beneficial effects of infliximab in reducing TNF-α levels and signs of inflammation (4, 7, 9, 15). Under our conditions, although not mentioned in the original study, the use of isotype control Abs in further experiments was not able to prevent signs of AIA and PD. Therefore, we do believe there is enough evidence in the literature to support the use of this tool to investigate the role of TNF-α in mice.

1
Qiu
W.
,
Wu
B.
,
Wang
X.
,
Buchanan
M. E.
,
Regueiro
M. D.
,
Hartman
D. J.
,
Schoen
R. E.
,
Yu
J.
,
Zhang
L.
.
2011
.
PUMA-mediated intestinal epithelial apoptosis contributes to ulcerative colitis in humans and mice
.
J. Clin. Invest.
121
:
1722
1732
.
2
Arruda
A. P.
,
Milanski
M.
,
Coope
A.
,
Torsoni
A. S.
,
Ropelle
E.
,
Carvalho
D. P.
,
Carvalheira
J. B.
,
Velloso
L. A.
.
2011
.
Low-grade hypothalamic inflammation leads to defective thermogenesis, insulin resistance, and impaired insulin secretion
.
Endocrinology
152
:
1314
1326
.
3
Mo
J. H.
,
Kang
E. K.
,
Quan
S. H.
,
Rhee
C. S.
,
Lee
C. H.
,
Kim
D. Y.
.
2011
.
Anti-tumor necrosis factor-alpha treatment reduces allergic responses in an allergic rhinitis mouse model
.
Allergy
66
:
279
286
.
4
Shi
J. Q.
,
Shen
W.
,
Chen
J.
,
Wang
B. R.
,
Zhong
L. L.
,
Zhu
Y. W.
,
Zhu
H. Q.
,
Zhang
Q. Q.
,
Zhang
Y. D.
,
Xu
J.
.
2011
.
Anti-TNF-α reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains
.
Brain Res.
1368
:
239
247
.
5
Brenndörfer
E. D.
,
Weiland
M.
,
Frelin
L.
,
Derk
E.
,
Ahlén
G.
,
Jiao
J.
,
Bode
J. G.
,
Sällberg
M.
.
2010
.
Anti-tumor necrosis factor α treatment promotes apoptosis and prevents liver regeneration in a transgenic mouse model of chronic hepatitis C
.
Hepatology
52
:
1553
1563
.
6
Simonaro
C. M.
,
Ge
Y.
,
Eliyahu
E.
,
He
X.
,
Jepsen
K. J.
,
Schuchman
E. H.
.
2009
.
Involvement of the Toll-like receptor 4 pathway and use of TNF-alpha antagonists for treatment of the mucopolysaccharidoses
.
Proc. Natl. Acad. Sci. USA
107
:
222
227
.
7
Xiong
W.
,
MacTaggart
J.
,
Knispel
R.
,
Worth
J.
,
Persidsky
Y.
,
Baxter
B. T.
.
2009
.
Blocking TNF-alpha attenuates aneurysm formation in a murine model
.
J. Immunol.
183
:
2741
2746
.
8
Crisafulli
C.
,
Galuppo
M.
,
Cuzzocrea
S.
.
2009
.
Effects of genetic and pharmacological inhibition of TNF-alpha in the regulation of inflammation in macrophages
.
Pharmacol. Res.
60
:
332
340
.
9
Wollin
M.
,
Abele
S.
,
Bruns
H.
,
Weyand
M.
,
Kalden
J. R.
,
Ensminger
S. M.
,
Spriewald
B. M.
.
2009
.
Inhibition of TNF-alpha reduces transplant arteriosclerosis in a murine aortic transplant model
.
Transpl. Int.
22
:
342
349
.
10
Fries
W.
,
Muja
C.
,
Crisafulli
C.
,
Costantino
G.
,
Longo
G.
,
Cuzzocrea
S.
,
Mazzon
E.
.
2008
.
Infliximab and etanercept are equally effective in reducing enterocyte APOPTOSIS in experimental colitis
.
Int. J. Med. Sci.
5
:
169
180
.
11
Choi
B.
,
Hwang
Y.
,
Kwon
H. J.
,
Lee
E. S.
,
Park
K. S.
,
Bang
D.
,
Lee
S.
,
Sohn
S.
.
2008
.
Tumor necrosis factor alpha small interfering RNA decreases herpes simplex virus-induced inflammation in a mouse model
.
J. Dermatol. Sci.
52
:
87
97
.
12
Cazanave
S.
,
Vadrot
N.
,
Tinel
M.
,
Berson
A.
,
Lettéron
P.
,
Larosche
I.
,
Descatoire
V.
,
Feldmann
G.
,
Robin
M. A.
,
Pessayre
D.
.
2008
.
Ibuprofen administration attenuates serum TNF-alpha levels, hepatic glutathione depletion, hepatic apoptosis and mouse mortality after Fas stimulation
.
Toxicol. Appl. Pharmacol.
231
:
336
343
.
13
Deveci
F.
,
Muz
M. H.
,
Ilhan
N.
,
Kirkil
G.
,
Turgut
T.
,
Akpolat
N.
.
2008
.
Evaluation of the anti-inflammatory effect of infliximab in a mouse model of acute asthma
.
Respirology
13
:
488
497
.
14
Al-Aly
Z.
,
Shao
J. S.
,
Lai
C. F.
,
Huang
E.
,
Cai
J.
,
Behrmann
A.
,
Cheng
S. L.
,
Towler
D. A.
.
2007
.
Aortic Msx2-Wnt calcification cascade is regulated by TNF-alpha-dependent signals in diabetic Ldlr-/- mice
.
Arterioscler. Thromb. Vasc. Biol.
27
:
2589
2596
.
15
Zalevsky
J.
,
Secher
T.
,
Ezhevsky
S. A.
,
Janot
L.
,
Steed
P. M.
,
O’Brien
C.
,
Eivazi
A.
,
Kung
J.
,
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D. H.
,
Doberstein
S. K.
, et al
.
2007
.
Dominant-negative inhibitors of soluble TNF attenuate experimental arthritis without suppressing innate immunity to infection
.
J. Immunol.
179
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1872
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.
16
Palframan
R.
,
Airey
M.
,
Moore
A.
,
Vugler
A.
,
Nesbitt
A.
.
2009
.
Use of biofluorescence imaging to compare the distribution of certolizumab pegol, adalimumab, and infliximab in the inflamed paws of mice with collagen-induced arthritis
.
J. Immunol. Methods
348
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36
41
.
17
Pinto
L. G.
,
Cunha
T. M.
,
Vieira
S. M.
,
Lemos
H. P.
,
Verri
W. A.
 Jr
,
Cunha
F. Q.
,
Ferreira
S. H.
.
2010
.
IL-17 mediates articular hypernociception in antigen-induced arthritis in mice
.
Pain
148
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.
18
Sachs
D.
,
Coelho
F. M.
,
Costa
V. V.
,
Lopes
F.
,
Pinho
V.
,
Amaral
F. A.
,
Silva
T. A.
,
Teixeira
A. L.
,
Souza
D. G.
,
Teixeira
M. M.
.
2011
.
Cooperative role of tumour necrosis factor-α, interleukin-1β and neutrophils in a novel behavioural model that concomitantly demonstrates articular inflammation and hypernociception in mice
.
Br. J. Pharmacol.
162
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83
.