Table 1 Immunomodulating therapies to prevent stroke-associated pneumonia and infections
Mechanism of action | Reference | Drug | Time of administration | Type of study | Major findings |
|---|---|---|---|---|---|
Inhibition of the SNS | Prass et al. 2003 [18] | Propanolol | Immediately before and also 4 and 8 h after MCAO. | Experimental (MCAO mice) | Prevention of lymphocyte apoptosis, lymphopenia, monocytic deactivation and changes in lymphocyte cytokine production; prevention of bacteremia and pneumonia; ↑ survival rates |
Wong et al. 2011 [33] | Propanolol and 6-OHDA | 24 h after MCAO | Experimental (MCAO mice) | Reversion of the iNKT cell phenotype induced by MCAO; ↑ survival rates; ↓ bacterial load in blood, lungs, liver, and spleen | |
Yan and Zhang 2014 [19] | Propanolol | Immediately before and also 4 and 8 h after MCAO. | Experimental (MCAO mice) | ↓ serum levels of MN, NMN and IL-10; ↑ pro-inflammatory cytokines; ↑ spleen volume | |
Deng et al. 2016 [79] | 6-OHDA | 3 days before MCAO | Experimental (MCAO rats) | Reversion of the expression of MHC class II; ↑ TNF-a and IFN-γ levels in LPS-stimulated macrophages in vitro; ↓ NF-κB activation; ↑ β-arrestin2 expression | |
Sykora et al 2015 [80] | β1-selective BBs, nonselective BBs | Before and after stroke | Clinical | ↓ frequency of pneumonia; association of post-stroke BB treatment with mortality | |
Maier et al. 2015 [81] | BBs (mainly metoprolol and bisoprolol) | Before and after stroke | Clinical | No differences in the risk of pneumonia; ↓ mortality. | |
Maier et al. 2018 [82] | BBs | Before and after stroke | Clinical | No differences in the rates of pneumonia nor mortality | |
Inhibition of the HPA axis | Prass et al. 2003 [18] | RU486 | 24 h, 5 h, and immediately before MCAO | Experimental (MCAO mice) | Prevention of lymphocyte apoptosis, lymphopenia, and monocytic deactivation |
Immunomodulation of iNKT cells | Wong et al. 2011 [33] | α-GalCer | 24 h after MCAO | Experimental (MCAO mice) | ↑ systemic levels of IFN-γ; ↓ stroke-induced neutrophil pulmonary influx and lung edema; ↓ bacterial load in blood, lungs, liver and spleen |
Inhibition of CD147 | Jin et al. 2019 [83] | CD147 antibody | 4 h after MCAO | Experimental (MCAO mice) | ↓ lung damage; ↓ lung leukocyte infiltration; ↓ plasma and lung IL-17A |
Inhibition of PTEN | Guan et al. 2013 [84] | Bvp | 24 h after MCAO | Experimental (MCAO mice) | ↓ bacterial loads in lung of bpv-treated mice; restoration of akt activation in the lung; ↓ mortality |
GM-CSF | Dames et al. 2018 [85] | Recombinant mGM-CSF | 6, 30, and 54 h after MCAO | Experimental (MCAO mice) | ↑ leukocyte counts in lung; ↑ WBC count; ↑ long-term outcome |