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Table 2 Methods and results from in vivo studies of cytokines

From: The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ

Cytokinesa

Animals

Main AD-like Pathology and initiating time

Cytokines Expression System

Expression Duration

Resultsb

Ref.

Delivery Method

Administration Routes

Immuno-histochemistry

Behaviors

IL-1β

3xTg AD mice (9 months old)

Aβ plaque: 6 mo. Tau: 12 -15 mo.

anti-IL-1R blocking antibody

Peritoneal Injection

every 8-9 days for 6 months

Aβ deposition ↓; Tau phosphorylation ↓

Cognition ↑

[83]

Rats adult

-

IL-1β injections

Cerebral ventricles

1 d

TNF-α, IL-10 ↑

No significance

[34]

8 d

TNF-α, IL-1β ↑ IL-10 ↓; APP mRNA ↑

Memory ↓

3xTg AD mice (8 months old)

Aβ plaque: 6 mo. Tau:12 -15 mo.

IL-1β-XAT cassette

Subiculum

1 and 3 mo.

Aβ deposition ↓; Tau phosphorylation ↑

\

[41]

APPswe/PSEN1dE9 mice (8 months old)

Aβ plaque: 6 mo.

rAAV2-IL-1β

Hippocampi

1 mo.

Aβ deposition ↓

\

[42]

IL-6

TgCRND8 mice (0 -12 h old (P0)/36 -48 h old (P2))

Early Aβ plaque: 3mo. Dense-cored plaques: 5 mo.

rAAV2/1-IL-6

Cerebral ventricles

5 mo.

Aβ deposition ↓

\

[46]

TgCRND8 mice (4 mo.)

rAAV2/1-IL-6

Hippocampi

1-1.5 mo.

Aβ deposition ↓

\

Tg2576 mice (P0)

Numerous Aβ plaques:11-13 mo.

rAAV2/1-IL-6

Hippocampi

3 mo.

Aβ deposition ↓

\

IL-4

Tg2576 + PS1 mice (3 months old)

Aβ plaques: 6 mo.

rAAV2/1-IL-4

Hippocampi

5 mo.

Aβ↓; Gliosis ↓; Neurogenesis ↑

Spatial learning ↑

[54]

TgCRND8 mice (4 months old)

Early Aβ plaque: 3 mo.

rAAV2/1-IL-4

Hippocampi

1.5 mo.

Aβ↑; Gliosis ↑

\

[55]

APPswe/PSEN1dE9 mice (3 months old)

Aβ plaque: 6 mo.

rAAV2/1-IL-4

Frontal cortex, Hippocampi

43 d.

Aβ↓ with no significance; Enhanced M2a phenotype of microglia

\

[56]

IL-10

APPswe/PSEN1dE9 mice (3 months old)

Aβ plaques: 6 mo.

rAAV2/1-IL-10

Hippocampi

5 mo.

Aβ =; Gliosis ↓; Neurogenesis ↑.

Spatial learning ↑

[52]

TgCRND8 mice (P0/P2)

Early Aβ plaque: 3mo.

rAAV2/1-IL-10

Cerebral ventricles

6 mo.

Aβ deposition ↑

Cognition ↓

[51]

Tg2576 mice (8 months old)

Numerous Aβ plaques: 11-13 mo.

rAAV2/1-IL-10

Hippocampi

5 mo.

Aβ deposition ↑

Cognition ↓

APPswe/PSEN1dE9 mice

Aβ plaque: 6 mo.

Bred with IL-10 KO mice

The whole body

12-13 mo.

Aβ deposition ↓

Cognition ↑

[53]

IL-12/IL-23

APPswe/PSEN1dE9 mice

Aβ plaque: 6 mo.

Bred with p40 (IL-12 and IL-23 shared) KO, p35 (IL-12) KO or p19 (IL-23) KO mice

The whole body

4 mo.

Aβ deposition ↓ (especially with p40 KO)

Cognition ↑

[65]

Senescence accelerated mouse (SAMP8) mice (6 months old)

Accelerated aging.

siRNA KO of p40

Dorsal third ventricle

1 mo.

Aβ deposition ↓

Cognition ↑

[66]

TNF-α

TgCRND8 mice (4 months old)

Early Aβ plaque: 3 mo.

rAAV2/1-TNF-α

Hippocampi

1.5 mo.

Aβ deposition ↓

\

[40]

3xTg AD mice (10, 17 months old)

Aβ plaque: 6 mo. Tau: 12 -15 mo.

TNF-α-lowering agent (3,6'-dithiothalidomide)

Peritoneal Injection

1.5 mo.

APP, Aβ peptide and Aβ deposition ↓; Tau phosphorylation ↓

Cognition ↑

[37]

3xTg AD mice (6 months old)

TNF-α-lowering agent (IDT)

Oral administration

10 mo.

Fibrillar Aβ↓; PHF-tau ↓

Cognition ↑

[39]

TGF-β

hAPP J9 line mice

Aβ plaques :5-7 mo.

Bred with transgenic expressing astrocytes-induced TGF-β1 mice

Brain

12-15 mo.

Aβ deposition ↓; Perivascular Aβ deposition ↑

\

[57]

Transgenic mice with inducible neuron-specific expression of TGF-β1 (3 months old)

-

The heterologous tTA system

Neocortex, hippocampi, striatum

54 d

Perivascular Aβ deposition ↑

\

[62]

24 d

Death of neurons induced by 3-nitropropionic acid ↓

\

SD rats with Aβ1-42 injection in bilateral hippocampus

TGF-β1 injection 7 d after Aβ injection

Left cerebral ventricles

3d

APP ↓

Cognition ↑

[166]

SD rats with Aβ1-42 injection in bilateral hippocampus

TGF-β1 administration1h prior to Aβ injection

Cerebral ventricles

7 d

APP ↓; PP2A ↑; TNF-α, IL-1β, iNOS, IFN-γ, IL-2, IL-17 and IL-22 ↓.

Cognition ↑

[58]

TGF-β1 administration7 d after Aβ injection

Nares

7 d

PP2A ↑; IL-1β, iNOS, IFN-γ, IL-2 and IL-17 ↓.

Cognition ↑

IFN-γ

APP Tg J20 mice

Aβ plaques : 5-7 mo.

Bred with Tg SJL mice expressing IFN-γ

The whole body

9 mo.

Oligodendrogenesis ↓

\

[167]

3xTg AD mice (2 months old)

Aβ plaque: 6 mo. Tau:12 -15 mo.

rAAV2/1- IFN-γ

Hippocampi

10 mo.

Aβ deposition ↑; Tau phosphorylation ↓

\

[168]

TgCRND8 mice P2

Early Aβ plaque: 3mo. Dense-cored plaques: 5 mo.

rAAV2/1- IFN-γ

Cerebral ventricles

5 mo.

Aβ deposition ↓; Gliosis ↑; Complement expression ↑; Peripheral monocytes infiltration ↑

\

[63]

TgCRND8 mice (4 months old)

Hippocampi

1.5 mo.

JNPL3 mice (P2), rTg4510 mice (P2)

Tau:4 mo.

rAAV2/1- IFN-γ

Cerebral ventricles

3 mo.

Soluble tau phosphorylation ↑

\

[87]

  1. Abbreviation: PHF-tau Paired helical filament tau, KO knockout
  2. aCytokines with controversial results are in bold.
  3. b↑: increase or improve, ↓: decrease or exacerbate, =: no change, \: no data
  4. For more detailed information for the model animals mentioned above, please refer to http://www.alzforum.org/research-models [169]