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. 2022 Apr 21;10(5):962. doi: 10.3390/biomedicines10050962

Table 1.

Experimental studies of VPA treatment effectiveness on immune-inflammation in vivo and in vitro.

# Experimental Model Animals/Cells Sex VPA Treatment Effect Ref.
1. Lung injury model Wistar rats males ↓ M1 macrophage proliferation and
↑ the M2 macrophages proliferation in the rat lung;
↓ inflammation;
↑ tissue repair		 [119]
2. Lung inflammation model Balb/c mice females ↓ cigarette-smoke induced neutrophil influx;
working as the PE inhibitor;
↓ inflammatory lung disorders		 [118]
3. Klebsiella pneumonia sepsis model BALB/c mice females ↓ immune cells capacity to induce a proinflammatory response [121]
4. Sublethal model of hemorrhagic shock Wistar Kyoto rats males ↓ hemorrhagic shock activated pro-inflammatory MAPK pathways;
↓ pulmonary neutrophil infiltration		 [120]
5. Chronic lung inflammation model A/J mice females ↓ neutrophils infiltration in the bronchoalveolar fluid [118]
6. Coxsackie B3 virus myocarditis model BALB/c mice males ↓ splenic Th17 and stimulated Treg cells;
↑ T cells apoptosis;
↓ IL-17A expression,
↑ IL-10 in serum and heart tissues;
↓ myocardial damage		 [122]
7. Post-operative inflammation the model of conjunctival scarring; Conjunctival inflammation model NIH3T3/BL6 mice males and females ↓ recruitment of a D45highF4/80low macrophages;
↓ chemokine and cytokine levels in tissues;
↓ tissue NF-кB2 p100 levels;
↓ TNF-α induction of chemokines, cytokines and NF-кB2 p100 expression;
↓TNF-α stimulation of NF-кB		 [123]
8. Spinal cord injury model BALB/c mice males ↓ macrophages infiltration, apoptotic cell death and caspase 3 activation;
↓ the lesion volume and improved functional recovery after spinal cord injury		 [124]
9. Acute DSS-induced colitis model C57BL/6J mice females disease amelioration was associated with prevention weight loss,
↓in histological signs of inflammation,
↓ IFN-γ and IL-6		 [125]
10. Experimental autoimmune encephalomyelitis model C57BL/6 mice females ↓ CD4+ T-lymphocyte infiltrates, associating with caspase 3 mediated apoptosis [126]
11. A model of LPS-provoked septic shock Sprague-Dawley rats males ↓ multiple organ damage caused by LPS induced septic shock [127]
12. Carrageenan-induced peritonitis model Wistar rats males ↓ by 92% leukocytes migration to the peritoneal cavity in a rat peritonitis;
↓ TNF-α, IL-1β, IL-6 levels, ROS generation		 [129]
13. Hemorrhagic shock model Sprague-Dawley rats males ↑ early survival, lung, liver and brain function [128]
14. Kidney ischemic/reperfusion injury model Wistar rats males ↑ blood IL-10 and TGF-β mRNA levels;
↑ direct correlation between IL-1β and TNF-α mRNA expression and IL-10 with TGF-β levels indicate the anti-inflammatory effect;
↓ kidney ischemic changes;
↓ serum creatinine level 		[130]
15. ARDS model C57BL6 mice males ↓ neutrophil influx into the lungs;
↓ local tissue destruction;
↓ the pulmonary and systemic inflammatory response 		[131]
16. Lung fibrosis model C57BL/6J mice males ↓ TGF-β1 in alveolar epithelial cells;
alleviate lung fibrosis 		[132]
17. Gl. thymus model Wistar rats males and
female		 ↑ SLC5A8 gene expression in gonad intact female thymocytes;
↓ SLC5A8 gene expression in gonad intact male thymocytes		 [133]
Cell model in vitro
18. BHK-21 cells Baby hamster kidney fibroblasts unknown ↓ replication of enveloped viruses [134]
19. Vero cells African green monkey kidney unknown ↓ replication of enveloped viruses [135]
20. RAW264.7 macrophage cells Mice unknown ↓ macrophage-mediated Th1 effector,
↑ Th2 effector cell activation, affects the phenotype and function of macrophage (M1/M2)		 [136]
21. Bone marrow-derived macrophages BALB/c mice females ↓ the production of TNF-α, IL-6 [137]
22. Bone marrow–derived primary macrophages (BMMs) C57BL/6
BALB/c mice		 females polarises macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype;
↓ IL-12 production and TNF-α by LPS-induced macrophage,
↑ IL-10 expression		 [121]
23. Alveolar epithelial cell line A549 unknown ↓ TGF-β1-induced EMT in alveolar epithelial cells [132]
24. PBMCs of healthy subjects Human unknown ↑ apoptosis of normal human CD4+ and CD8+ T cells [138]
25. Monocytic leukemia THP-1 cells Human unknown ↓ LPS-induced production of TNF-α, IL-6 [126]
26. Dendritic cells derived from monocytes of healthy blood donors’ Human unknown ↓ monocyte differentiation into DCs;
↓ secretion of IL-8, IL-1b, IL-6, TNF-α and IL-10		 [134]
27. Healthy blood donors T CD8+ lymphocytes Human males +
females (combined)		 ↓ in cellular proliferation [139]

↓ decreased; ↑ increased.