Autoimmune diseases occur when our immune system attacks and destroys our own cells and tissues due to breakdown of tolerance. Immune-mediated inflammatory disease (IMID) is a group of disorders that covers a large number of disease indications thought to be related to each other through similar mechanisms of immune-system dysfunction and dysregulation. Animal models provide insights into underlying pathologies, etiologies, and specific signaling pathways of human diseases because of their physiological similarities to humans and their shorter disease progression that allows the entire disease onset and development to be studied within a relatively short amount of time. https://www.medicilon.com/blog/featured-stories/inflammatory-immune-models/
1. MEDICILON
Autoimmune diseases occur when our immune system attacks and destroys our own cells and tissues due to
breakdown of tolerance. Immune-mediated inflammatory disease (IMID) is a group of disorders that covers a
large number of disease indications thought to be related to each other through similar mechanisms of
immune-system dysfunction and dysregulation. Animal models provide insights into underlying pathologies,
etiologies, and specific signaling pathways of human diseases because of their physiological similarities to
humans and their shorter disease progression that allows the entire disease onset and development to be
studied within a relatively short amount of time.
Medicilon maintains a large in-house library of animal disease models to meet the research demands in differ-
ent therapeutic areas. Medicilon provides a number of validated models of inflammatory and autoimmune
diseases. Equipped with Ph.D. level scientists as well as the most innovative technology and platforms. Medi-
cilon is committed to providing high-quality customer-oriented service support and delivering high-quality
results. The Pharmacology department combines strong technical expertise with extensive experience in
consulting, conducting, and evaluating efficacies of small molecule and biologic drugs, we can provide efficacy
evaluation for a variety of autoimmune diseases using a wide variety of in vitro and in vivo research models.
The Models Medicilon Offer
EAE experimental allergic encephalomyelitis model
Psoriasis model induced by Imiquimod
IL-23 induced mouse auricle psoriasis model
Collagen induced arthritis (CIA) model
CFA induced arthritis (AIA) model
Gouty arthritis model induced by Sodium urate
Arthritis
Amyotrophic lateral sclerosis (ALS)
Psoriasis
Diseases Models
2. 0
1
2
3
4
5
6
7
8
9
12 14 16 19 22 26 28
Foot
volume
(ml)
Days
Naive
Vehicle
Evobrutinib 2.5 mg/kg
Tofacitinib 2.5 mg/kg
Test article low dose
Test article middle dose
Test article high dose
Foot
volume
(mL)
0
2
4
6
8
10
12
14
12 14 16 19 22 26 28
Arthri�s
Index(AI)
Days
Naive
Vehicle
Evobrutinib 2.5 mg/kg
Tofacitinib 2.5 mg/kg
Test article low dose
Test article middle dose
Test article high dose
Medicilon Case: CIA model
Days
Arthritis
Index(AI)
Days
MEDICILON
Complete Freund’sAdjuvant (CFA) InducedArthritis (AIA) Model
Rheumatoid arthritis (RA) is a chronic progressive inflammatory arthritis. Among other models of arthritis in
rodents, CFA induced model displays various similarities with that of human arthritis which makes it most
suitable model for inducing arthritis. CFA is a suspension of dessicated mycobacterium in paraffin oil and man-
nide monooleate that induces inflammation, tissue necrosis, and ulceration. CFA can be used subcutaneously
in the paw, or intraperitonealy in mice and rats. CFA-induced arthritis model represents persistent inflamma-
tion with numerous systemic alterations as well as synovial hyperplasia, ear and tail "arthritis" nodules, etc.
CFA-induced arthritis has been used as a model of sub-chronic or chronic inflammation in rats and is of
considerable relevance for the study of pathophysiological and pharmacological control of inflammatory
processes, as well as the evaluation of analgesic potential or anti-inflammatory effects of drugs.
Collagen Induced Arthritis (CIA) Model
Animal models of rheumatoid arthritis (RA) are essential for studying the pathogenesis of RA in vivo and deter-
mining the efficacy of anti RA drugs. The CIA model is the most commonly studied autoimmune model of rheu-
matoid arthritis. CIA model can be widely used to address questions of disease pathogenesis and to validate
therapeutic targets. CIA can be induced in susceptible strains of rodents and NHPs by immunization with type
II collagen (CII). Following immunization, these animals develop an autoimmune-mediated polyarthritis that
shares several clinical, histological, and immunological features with the human autoimmune disease rheuma-
toid arthritis. As with RA, susceptibility to CIA in rodents is linked to the class II molecules of the major histo-
compatibility complex (MHC). The immune response to CII is characterized by both the stimulation of colla-
gen-specific T cells and the production of high titers of antibody specific for both the immunogen (heterologous
CII) and the autoantigen (mouse or rat CII). Because of the important similarities between CIA and rheumatoid
arthritis, this experimental model of autoimmune arthritis has been extensively used to research the mecha-
nism of anti RA drug and evaluate the efficacy new drugs.
Chronic atopic dermatitis model induced by DNFB
TNBS induced rat ulcerative colitis model
DSS induced mouse ulcerative colitis model
Atopic dermatitis (AD)
Inflammatory bowel disease (IBD)
Subacute eczema-like model induced by DNFB
Acute eczema-like model induced by Phorbol ester
3. 0
10
20
30
40
50
60
70
80
90
100
110
120
130
IL-6 IL-1β IFN-γ
The
Levels
of
IL-6,
IL-1β,
IFN-γ
(pg/mL)
The Levels of IL-6, IL-1β, IFN-γ in Serum
Control vehicle
Model vehicle
Test ar�cle 1mg/kg
Test ar�cle 3mg/kg
Test ar�cle 10mg/kg
Tofaci�nib 3mg/kg
**
**
**
*
**
**
**
**
**
**
**
**
**
**
0
1
2
3
4
5
6
7
Day15 Day17 Day21 Day24 Day27 Day29 Day31
Hind
Feet
Arthritis
Index
Hind Feet Arthritis Index Control vehicle
Model vehicle
Test article 1mg/kg
Test article 3mg/kg
Test article 10mg/kg
Tofacitinib 3mg/kg
** ** ** ** ** ** **
** **
** **
**
**
**
** **
**
**
**
**
**
0
1
2
3
4
5
6
7
8
day15 day17 day21 day24 day27 day29 day31
Hind
Feet
Volume(mL)
Hind Feet Volume(mL)
Control vehicle
Model vehicle
Test article 1mg/kg
Test article 3mg/kg
Test article 10mg/kg
Tofacitinib 3mg/kg
** ** ** ** ** ** **
** **
**
** **
*
**
** ** **
**
** **
**
MEDICILON
Medicilon Case: CFA induced arthritis (AIA) model
Hind Feet Volume (mL)
Hind
Feet
Volume
(mL)
Hind
Feet
Arthritis
Index
Hind Feet Arthritis Index
The
Levels
of
IL-6,
IL-1β,
IFN-γ
(pg/mL)
The Levels of IL-6, IL-1β, IFN-γ in Serum
4. 1.80
1.90
2.00
2.10
2.20
2.30
2.40
2.50
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96
Foot
volume
(ml)
Time (h)
Vehicle i.g.
Colchicine i.g.
Foot volume (ml)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96
Inflammation
index
score
Time(h)
Vehicle i.g.
Colchicine i.g.
Inflammation index score
MEDICILON
Medicilon Case: Gouty arthritis model induced by Sodium urate
Gouty arthritis is an inflammatory joint disease. The inflammatory process is initiated by the deposition of
monosodium urate (MSU) crystals in the surrounding tissue. Gout is accompanied by tenderness, erythema,
redness, swelling, pain, and fever in periarticular tissues or in joints. Sodium urate can be used to induce acute
gouty arthritis model.
MSU crystal-induced inflammatory disorder is well-represented in the gout disease model; neutrophil infiltra-
tion into the inflamed joints is the most distinctive phenotype. MSU crystal-induced intracellular signaling gen-
erates acute joint inflammation and mediates neutrophil migration and activation. The progression of sterile
inflammation in acute gouty arthritis is promoted by an auto-amplification loop of the inflammation.
Gouty Arthritis Model Induced by Sodium Urate
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by neu-
roinflammation with consequent demyelination and axonal degeneration. EAE is the most widely used experi-
mental model for MS.
EAE mice are used to model the disease progression of MS and mirror MS-like pathology. EAE mice also
exhibit cognitive deficits, dyskinesia and significant disruption in the structural integrity of synapses. EAE is a
complex condition in which the interaction between a variety of immunopathological and neuropathological
mechanisms leads to an approximation of the key pathological features of MS: inflammation, demyelination,
axonal loss and gliosis. Moreover, EAE is often used as a model of cell-mediated organ-specific autoimmune
conditions in general. EAE has a complex neuropharmacology, and many of the drugs that are used in MS
have been developed, tested or validated on the basis of EAE model.
Experimental Autoimmune Encephalomyelitis (EAE) Model
Inflammation
index
score
Inflammation index score
Foot
volume
(mL)
Foot volume (mL)
Time (h) Time (h)
5. -2.0
0.0
2.0
4.0
6.0
8.0
D0 D4 D5 D6 D7 D8
Skin
colligation
score
days
Skin colligation score of mice
Control
Model
Posi�ve drug
Test ar�cle low
Test ar�cle middle
Test ar�cle high
0.0
0.1
0.1
0.2
0.2
0.3
0.3
0.4
0.4
0.5
0.5
D0 D1 D2 D3 D4 D5 D6 D7 D8
Skin
thichness
(mm)
days
Skin thickness of mice
Control
Model
Posi�ve drug
Test ar�cle low
Test ar�cle middle
Test ar�cle high
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
D0 D11 D12 D14 D15 D17 D19 D20 D21 D22 D23 D25 D27 D29
Clinical
Score
Day a�er immuniza�on
Clinical score of EAE model in C57BL/6 mice
Vehicle
FTY720 3mg/kg po QD
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
15.0
17.0
19.0
21.0
23.0
25.0
27.0
D0 D2 D4 D6 D8 D10 D12 D14 D15 D17 D19 D22 D23 D25 D27 D29
Body
weight(g)
Day a�er immuniza�on
Body weight of EAE model in C57BL/6 mice
Vehicle
FTY720 3mg/kg po QD
*
* *
*
*
* *
*
*
*
*
* *
*
*
*
MEDICILON
Day after immunization
Body
weight(g)
Psoriasis is a chronic inflammatory skin disease associated with multiple contributing factors including autoim-
mune dysfunction. Psoriasis leads to the alteration of skin components which generally manifests as unwant-
ed topical symptoms. One of the most widely approved psoriasis-like animal models is the Imiquimod
(IMQ)-induced mouse model. The IMQ-induced Psoriasis model is particularly translational into the clinic as it
has many of the significant markers of human disease, including histopathology of lesions and strong activa-
tion of the immune system. IMQ is a ligand for Toll-like receptors 7/8 which activates macrophages, monocytes
and dendritic cells.
Topical application of IMQ can induce psoriasis. It is a rapid and convenient model that allows the elucidation
of underlying mechanisms and the evaluation of new therapies against psoriasis.
Psoriasis Model Induced by Imiquimod
Medicilon Case: EAE experimental allergic encephalomyelitis model
Medicilon Case: Psoriasis model induced by Imiquimod
Skin colligation score of mice
Clinical
Score
Day after immunization
Body weight of EAE model in C57BL/6 mice Clinical score of EAE model in C57BL/6 mice
Skin
colligation
score
days
Skin thickness of mice
Skin
thichness
(mm)
days
6. MEDICILON
Treatment
C57BL/6 mice
Control
Model
BALB/C mice
Medicilon Case: Psoriasis model induced by Imiquimod
Pathology score of mice skin
Pathology
score
IL-23 Induced Mouse Auricle Psoriasis Model
IL-23 is a heterodimeric cytokine composed of two disulfide-linked subunits, a p19 subunit that is unique to
IL-23, and a p40 subunit that is shared with IL-12. IL-23 is produced by various immune cells, and stimulates
the activity of Th17 cells. Th17 cells, in turn, produce cytokines that promote inflammation and recruit immune
cells to the site of infection or injury. The IL-23/IL-17A pathway plays a critical role in psoriasis. IL-23 is a key
cytokine produced by antigen-presenting cells that is necessary for the development of pathogenic IL-17A-se-
creting lymphocytes. IL-17A and other cytokines such drive the abnormal differentiation of keratinocytes and
inflammation that lead to the manifestations of disease.
Degree of Keratinization
Epidermal thickness
Leather thickness
Inflammatory infiltrate
Total score
7. IL-23-induced psoriasis mouse model is the most prevalent among psoriatic mouse models due to its ease of
use, convenience, and low cost. IL-23 induced psoriasis mouse mode is provoked by IL-23 intra-dermal injec-
tions produces a cutaneous phenotype in mice frequently studied as an acute model of human psoriasis. The
IL-23 injection model has the advantage of using a single cytokine that is of established importance in psoria-
sis in initiating inflammation.
MEDICILON
Ear
thickness
(mm)
Several factors have been implicated in atopic dermatitis. Symptoms include itchiness, redness, and dryness
of the skin. If left unchecked this inflammatory processes may contribute to a wide variety of human disease
processes. Inappropriate inflammation is usually treated with certain steroids such as glucocorticoids or with
non-steroidal anti-inflammatory drugs. Both classes of compounds can have undesirable side effects. Discov-
ering new ways to treat inflammation is of clinical importance.
Acute Eczema-like Model Induced by Phorbol Ester
0.0
0.1
0.2
0.3
0.4
0.5
0.6
D0 D2 D4 D6 D8
Ear
thickness
(mm)
Days
Control
Model
Posi�ve sample 16mg/kg
Test sample 16mg/kg
Test sample 8mg/kg
Test sample 4mg/kg
Ear thickness of mice
0
1
2
3
4
5
6
7
8
D0 D2 D4 D6 D8
Pathology
score Days
Control
Model
Positive sample 16mg/kg
Test sample 16mg/kg
Test sample 8mg/kg
Test sample 4mg/kg
Pathology score of mice ear
Medicilon Case: IL-23 induced mouse auricle psoriasis model
Control
Model
C57BL/6 mice
Ear thickness of mice
Days
Pathology
score
Pathology score of mice ear
Days
8. 0.2
0.3
0.4
0.5
0.6
0.7
0' 1h 2h 4h 6h 20h 24h
Auricle
thickness(mm)
Time
Thickness of the ear
Control
Posi�ve Drug
Test ar�cle H dose
Test ar�cle M dose
Test ar�cle L dose
Model
MEDICILON
Subacute Eczema-like Model Induced by DNFB
Several studies have tried to establish mice models of atopic dermatitis (AD) through the allergen of Dermato-
phagoides farinae (Df). However, there are no typical skin lesions after epicutaneous application of an extract
of Df (DfE) on BALB/c mice. Dinitrofluorobenzene (DNFB) is a common hapten that brings about contact
dermatitis in mice. The integrity of mice skin gets disrupted when DNFB recruits the cytotoxic T lymphocytes
to the skin, inducing keratinocyte apoptosis. Skin dysfunction induced by DNFB may be a way to enhance the
effects of DfE on mice skin.
Alternating epicutaneous exposure to DNFB and DfE can produce AD-like models with typical clinical features
and Th2-type immune responses in BALB/c mice. This model could be valuable for studying the pathogenesis
of AD and developing novel therapeutic agents for it.
Medicilon Case: Subacute eczema-like model induced by DNFB
Groups
Ear
swelling
(%)
To induce an inflammatory response, a mouse model of Phorbol Ester-induced inflammation can be used.
Phorbol Ester is often used as a potent inducer of sterile inflammation in screening for the relative activity of
potential anti-inflammatory drugs. Phorbol Ester can be used in animal modeling to construct acute eczema-
like models.
Medicilon Case: Acute eczema-like model induced by Phorbol ester
0
5
10
15
20
25
1
Ear
swelling
(%)
Groups
Swelling of the ear
Control
Posi�ve drug
Test ar�cle H dose
Test ar�cle M dose
Test ar�cle L dose
Model
**
**
**
**
Swelling of the ear
Groups
Ear
swelling
(%)
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0' 1h 2h 4h 6h 20h 24h
Auricle
thickness(mm)
Time
Thickness of the ear
Control
Posi�ve drug
Test ar�cle H dose
Test ar�cle M dose
Test ar�cle L dose
Model
Thickness of the ear
Time
Auricle
thickness
(mm)
Thickness of the ear
Auricle
thickness
(mm)
Time
0
1
2
3
4
5
6
7
8
9
10
1
Ear
swelling
(%)
Groups
Swelling of the ear
Control
Posi�ve Drug
Test ar�cle H dose
Test ar�cle M dose
Test ar�cle L dose
Model
***
***
***
***
Swelling of the ear
9. MEDICILON
BALB/C mice
Control
Model
Medicilon Case: Chronic atopic dermatitis model induced by DNFB
Skin thickness
0.0
0.2
0.4
0.6
0.8
1.0
1.2
Skin thickness(mm)
Skin
thickness(mm,Mean±SEM)
Control
Model
Posi�ve drug
Test ar�cle H
Test ar�cle M
Test ar�cle L
###
***
*** ***
***
Skin thickness
Skin thickness (mm)
Skin
thickness
(mm,Mean±SEM)
0
1
1
2
2
3
3
4
4
5
D0 D2 D4 D6 D8
Skin
Score
(Mean±SEM)
Skin Score
Control
Model
Posi�ve drug
Test ar�cle H
Test ar�cle M
Test ar�cle L
###
###
***
***
***
***
***
***
***
Days
###
Days
Skin Score
Skin
Score
(Mean±SEM)
Chronic Atopic Dermatitis Model Induced by DNFB
Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease, characterized by severe itching
and recurrent skin lesions. Chronic itching is a sensation that triggers the desire to scratch. Repeated applica-
tions of 2,4-dinitrofluorobenzene (DNFB) were used to induce AD in a mouse model of annoying pruritus.
Application of DNFB could be used to build chronic atopic dermatitis model. DNFB successfully induces
AD-like dermatitis and histological changes as well as epidermal barrier dysfunction.
In the chronic phase of AD-like dermatitis, Th2-associated cytokines were still highly expressed, while Th1-
and Th17-associated cytokines were also gradually increased. Compared with the acute phase, the
JAK-STAT signaling pathway was highly expressed in the chronic phase of AD-like dermatitis. The JAK-STAT
signaling pathway plays a pivotal role in the chronicity of AD.
10. MEDICILON
Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic
inflammatory disorder of the intestinal tract whose etiology has not yet been fully elucidated. IBD pathogenesis
is multifactorial. IBD is characterized by massive cellular infiltrates which is associated with abnormalities of
the immune system including increased number of CD4+
T-lymphocytes, mast cells, neutrophils, and eosino-
phils. These conditions give rise to inflammation, ulceration, edema, diarrhea along with blood and/or mucus,
fever, and gastric dysmotility. No medical cure has been developed for IBD and the current treatment focuses
on maintaining remission. IBD animal models represent certain pathophysiological features of human UC and
CD involving weight loss and diarrhea accompanied by blood and/or mucus, fever, shortened colon, crypt
abnormalities, gastric dysmotility and infiltration of inflammatory cells.
The 2,4,6-Trinitrobenzenesulfonic acid (TNBS) murine model of colitis is a Th1 inflammation characterized by
infiltration of CD4+
lymphocytes that shares features with human CD and UC. In comparison with other animal
models of IBD, TNBS model is an efficient method. TNBS can mimic many of macroscopic and histological
characteristics of human IBD and is widely applicable to mice and rats.
TNBS Induced Rat Ulcerative Colitis Model
Medicilon Case: TNBS induced rat ulcerative colitis model
Colon length of rat Colon ulcer area of rat
Group Group
Colon
Length
(mm)
Ulcer
Area
(mm
2
)
Positive drug
Model
11. MEDICILON
Inflammatory bowel diseases (IBD) mainly comprised of Ulcerative Colitis and Crohn's Disease are complex
and multifactorial disease with unknown etiology. Two major IBD of the gastrointestinal tract, Crohn's Disease
(CD) and Ulcerative Colitis (UC), are characterized by both acute and chronic inflammation of the intestine
with multifactorial etiology. Dextran sodium sulfate (DSS) is a water-soluble, negatively charged sulfated poly-
saccharide with variable molecular weights. Administration of DSS in mice causes human ulcerative
colitis-like pathologies due to its toxicity to colonic epithelial cells, which results in compromised mucosal barri-
er function. The DSS colitis model is very popular in IBD research due to its rapidity, simplicity, reproducibility
and controllability. Acute, chronic and relapsing models of intestinal inflammation can be achieved by modify-
ing the concentration of DSS and the frequency of administration.
DSS Induced Mouse Ulcerative Colitis Model
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3 5
4 0
5 0
6 0
7 0
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**
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0 .16
0 .18
0 .20
0 .22
0 .24
**
Medicilon Case: DSS induced mouse ulcerative colitis model
Colon weight of mice Colon length of mice
Groups Groups
Medicilon Case: TNBS induced rat ulcerative colitis model
Pathology of colon of rat
12. MEDICILON
References:
[1] Jing Luan, et al. Applicability and implementation of the collagen-induced arthritis mouse model, including protocols (Review). Exp
Ther Med. 2021 Sep;22(3):939. doi: 10.3892/etm.2021.10371.
[2] Xin Cui, et al. Evaluation of antiarthritic activity of nimbolide against Freund's adjuvant induced arthritis in rats. Artif Cells Nanomed
Biotechnol. 2019 Dec;47(1):3391-3398. doi: 10.1080/21691401.2019.1649269.
[3] Su-Hyun Shin, et al. 1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol (PLAG) Mitigates Monosodium Urate (MSU)-Induced Acute
Gouty Inflammation in BALB/c Mice. Front Immunol. 2020 Apr 24:11:710. doi: 10.3389/fimmu.2020.00710.
[4] Cris S Constantinescu, et al. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J
Pharmacol. 2011 Oct;164(4):1079-106. doi: 10.1111/j.1476-5381.2011.01302.x.
[5] Leslie van der Fits, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol.
2009 May 1;182(9):5836-45. doi: 10.4049/jimmunol.0802999.
[6] Shujing Feng, et al. An Atopic Dermatitis-Like Mouse Model by Alternate Epicutaneous Application of Dinitrofluorobenzene and an
Extract of Dermatophagoides Farinae. Front Med (Lausanne). 2022 Jun 15:9:843230. doi: 10.3389/fmed.2022.843230.
[7] Benoit Chassaing, et al. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol. 2014 Feb
4:104:15.25.1-15.25.14. doi: 10.1002/0471142735.im1525s104.
Pathology of colon of mice
C on tr ol M od el S AS P H igh- do se M iddl e- dose L ow -d ose
Medicilon Case: DSS induced mouse ulcerative colitis model
General view of colon of mice
MEDICILON
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