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Table 1 Immunomodulatory effects of tetracyclines in preclinical and clinical models of acute respiratory distress syndrome (ARDS)

From: Immunomodulation by Tetracyclines in the Critically Ill: An Emerging Treatment Option?

Author

Year

Tetracycline

Model

Stimulants or pathogens

Immune response

Peukert et al. [5]

2021

Tetracycline

Mouse, human (ex vivo)

LPS, H1N1 influenza virus (mouse); viral, bacterial, and non-pulmonary ARDS (human)

IL-1ß, IL-18, caspase-1 activation, neutrophil influx ↓, survival ↑

Zhang et al. [20]

2019

Doxycycline

Mouse

Paraquat

MMP-9, MPO, neutrophil influx ↓

Wang et al. [24]

2014

Doxycycline

Rat

Cardiopulmonary bypass

TNF-α, IL-1ß, MMP-9 ↓

Zhang et al. [17]

2014

Doxycycline

Dog

Cardiopulmonary bypass

MMP-9, MPO, neutrophil influx ↓

Roy et al. [16]

2012

CMT-3

Pig

Ischemia by clamping of SMA, placement of fecal clot in peritoneum

TNF-α, IL-1ß, IL-6, IL-8, IL-10 ↓, MMP-2, -9, NE, survival ↔

Ng et al. [27]

2012

Doxycycline

Mouse

H3N2 influenza virus

MMP-2, MMP-9, T1-α, thrombomodulin, neutrophil influx ↓

Moon et al. [22]

2012

Doxycycline

Mouse

LPS

Syndecan-1 (MMP-7 substrate), neutrophil influx ↓

Zhou et al. [25]

2010

CMT-3

Sheep

3rd degree burn, smoke inhalation, barotrauma

MMP-2 ↓, MMP-9 ↔, survival ↑

Sochor et al. [21]

2009

Doxycycline

Rat

Acute pancreatitis (intraductal glycodeoxycholic acid, cerulein)

MMP-9, neutrophil influx ↓

Fujita et al. [26]

2007

Doxycycline

Mouse

LPS or Streptococcus pneumoniae

MMP-2, -9, neutrophil influx ↓, survival ↑

Kim et al. [14]

2006

CMT-3

Rat

Ventilation

MMP-9, MPO, neutrophil influx ↓

Fujita et al. [28]

2006

Doxycycline

Mouse

Bleomycin

MMP-2, -9, neutrophil influx ↓

Steinberg et al. [19]

2005

CMT-3

Pig

Ischemia by clamping of SMA, placement of fecal clot in peritoneum

IL-6, IL-8, IL-10, NE ↓, IL-1, MMP-2, -9, neutrophil influx ↔, survival ↑

Steinberg et al. [15]

2003

CMT-3

Rat

Cecal ligation and puncture

MMP-2, MMP-9 ↓, survival ↑

Carney et al. [23]

2001

CMT-3

Pig

LPS

MMP-2, MMP-9, neutrophil influx ↓

McCann et al. [29]

1999

CMT-3

Pig

Cardiopulmonary bypass, LPS

Neutrophil influx ↓

Carney et al. [13]

1999

CMT-3

Pig

Cardiopulmonary bypass, LPS

MMP-2, MMP-9, NE, neutrophil influx ↓, survival ↑

  1. ↑ significant increase, ↓ significant decrease, ↔ no significant difference, CMT-3 chemically modified tetracycline 3, IL interleukin, LPS lipopolysaccharide, MMP metalloproteinase, MPO myeloperoxidase, NE neutrophil elastase, SMA superior mesenteric artery, TNF-α tumor necrosis factor alpha, T1-α membrane protein of alveolar type I epithelium