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. 2019 Aug 22;2019:1365210. doi: 10.1155/2019/1365210

Table 1.

Systematic review of data search.

Source Subject Models
Interventions
Methods of analysis: mRNA measurement Methods of analysis:
Protein measurement
IL-6 measurement,
tissue
Microglia status, tissue Microglia IL-6 producer Outcome
IL-6 increased and microglia activated Wang, H.
2018
Viral-bacterial lung co-infection mice, adults/
primary microglial cell culture 
Influenza A, Streptococcus. pneumoniae, SAA exposure
qPCR - Hypothalamus and primary cell culture: Tnf, Il1b, Il6, Ccl2, Fpr2, Saa1 IHC - PVN: IBA1, GFAP, TNF-α, SAA mRNA expression increased, hypothalamus
(P < 0.05)
Activated, PVN
(P < 0.05)
Yes
(P < 0.05)
Neuroinflammation
Le Foll, C.
2015
Amylin exposure rats and mice, adults/
VMH explants/
VMH astrocytes/
VMN neurons/
cortical and hypothalamic microglia
Amylin exposure
qPCR - ARC, VMH, VMN, cell culture:: Il-1b, Il-6, Il-10, Tnf, Lif, Cntf, Gp130, Ctr1a, Ctr1b, Ramp1, Ramp2, Ramp3, Lepr-b, Socs3, Ins-r, Npy, Agrp, Pomc. ICC - ARC, VMN: pSTAT3
Immunoassay - cell culture medium: IL-1β, IL-6, IL-10, TNF-α
mRNA expression increased, VMN
(P < 0.05)
Activated, Cortical
( P < 0.05)
Yes Decreased body weight gain
Ziko, I.
2014
LPS exposure in adults Neonatally overfed rats, pups and adults
Neonatal overfeeding model
LPS exposure
qPCR - hypothalamus:  
Tlr4, Nfkb,Il1b, Il1ra, Il6, Tnf
IHC - DMH, LH, VMH: IBA1 mRNA expression increased, hypothalamus
(P < 0.05)
Activated, PVN
(P < 0.05)
No data Increased body weight in small litters and adults
Tapia-González, S.
2011
Neonatal overfeeding rats, pups
Neonatal overfeeding model
WB - hypothalamus: IL-6, p-IkB
IHC - ARC, ME, VMH: MHC-II
Protein expression increased, hypothalamus
(P < 0.01)
Activated, hypothalamus, (P<0,05) No data Overweight
Mingam, R.
2008
LPS exposure in P2X7R knockout model mice, adult/
primary glial cell culture
LPS exposure
qPCR - hypothalamus: Il-6, Il-1b, Tnf ELISA - cell culture medium: IL-1β
IHC - cell culture: CD11b, CD68, IL-1β, GFAP,
WB - cell culture medium: IL-1β
Protein and mRNA expression increased, whole brain
(P < 0.05)
Activated
(P < 0.05)
Yes
(P < 0.05)
Decreased IL-1β release

IL-6 increased without microglia information Cao, H. M.
2015
Mimecan exposure Rats and mice, adults
primary neurons cell culture
N9 cells
Mimecan exposure
qPCR - hypothalamus: Il1-b, Il-6
qPCR - primary cell culture: Il1-b, Il-6, Socs3
qPCR
qPCR -N9 cell culture: Il1-b, Il-6, Socs3
WB - hypothalamus: SOCS3 mRNA expression increased, hypothalamus
(P < 0.05 /
P < 0.01)
No data Yes
(P < 0.01)
Anorexia
Roque, A.
2015
Early life stress rats, pups
Maternal separation model
qPCR - hypothalamus: Il1-b, Il-6, Tnf - mRNA expression increased, hypothalamus
(P < 0.01)
No data No data Stress can dysregulate the HPA axis

IL-6 increase and microglia suppressed Silva, T.M.
2017
Minocycline in acute hypoxia rats, adults
Pretreatment with Minocycline followed by exposition to acute hypoxia
qPCR - mice PVH: Il-1b, Il-6, Tnf, Mmp9, Cd3, Hprt IHC: TH, c-Fos mRNA expression increased, PVH
(P < 0.05)
Suppressed
(P < 0.05)
No Disrupted organization of breath activity

IL-6 unaltered and microglia activated Younes-Rapozo, V.
2015
Long-term effects of nicotine exposure during lactation in offspring rats, pups
Nicotine in dams.
- IF - ARC, PVN, LH, PE: GFAP, IBA-1, CX3CR1, MCP-1, IL-6 Protein expression had no change, ARC, PE, PVN, LH Activated, in PVN (P < 0.05) No data Obesity
Sugama, S.
2007
Inescapable stress rats and mice, adults
restraint combined with water immersion stress
qPCR - hypothalamus: Il-1b, Il-6, Inos IF: IL1-β, IL-6, iNOS
IHC: OX42, CD11b
mRNA expression had no change, hypothalamus Activated
(P < 0.001)
No Hypothalamic microglia activation
Ye, S. M.
1999
Aging mice, juvenile, adult, and aged/
primary cell culture of whole brains
Basal conditions
RT-PCR - glial cell culture: Il-6 ELISA glial cell culture medium: IL-6
IHC: GFAP, MAC-1(CD11B)
Flow Cytometry glial cell culture: GFAP, MAC-1
ELISA tissue homogenates: IL-6
Hybridoma bioassay: IL-6
Protein expression had no change in the hypothalamus Activated, all brain (P < 0.05) Yes
(P < 0.01)
chronic inflammation in whole brain without changes in the hypothalamus

IL-6 decreased and microglia suppressed Ramirez, K.
2016
Benzodiazepines treatment in Repeated social stress condition Mice, adult
Exposed to stress condition and treated with benzodiazepines
qPCR - hypothalamus: Il1-b, Il-6, Tnf - mRNA expression decreased, hypothalamus
(P < 0.05)
Suppressed, whole brain
(P < 0.05)
Yes
(P < 0.05)
reversal of stress-induced behavioral
Santos Masson, G.
2015
Short-term exercise training in arterial hypertension model Rat, adult
2 weeks of exercise model in spontaneously hypertensive rats
- WB - PVN: CXCR4, ERK1/
2 pERK1/
2, HMGB1, IL-6, p-IKBa, SDF-1, TNF-α
IF: HMGB1, IBA-1
Protein expression decreased, PVN
(P < 0.01)
Suppressed, PVN
(P < 0.01)
No data Control of arterial hypertension

Legend: ARC: arcuate nucleus, LPS: lipopolysaccharide, HPA: hypothalamic–pituitary–adrenal ME: median eminence, PVN: paraventricular nucleus, SAA: serum amyloid A, VMH: ventromedial hypothalamus, VMN: ventromedial nucleus.