Hypertonic saline modulates innate immunity in a model of systemic inflammation.
We sought to determine if hypertonic saline (HTS) impacted alveolar macrophage (AM) activation and intracellular inflammatory gene signaling in a model of systemic inflammation. Rats received an intravenous administration of 4 mL/kg of 7.5% HTS or L-lactate lactated Ringer's (L-LR). They were simultaneously treated with an intraperitoneal injection of zymosan, which induces noninfectious systemic inflammation. AM were harvested by bronchoalveolar lavage 24 h after treatment. AM activation was analyzed by measurement of baseline and lipopolysaccharide (LPS)-induced TNF-alpha production. Intracellular signaling was analyzed for activation of the mitogen-activated protein kinases (MAPKs): ERK1/2, JNK, and p38. AM from HTS-treated rats produced less TNF-alpha than from L-LR-treated rats (927 +/- 335 pg/mL [SEM] vs. 3628 +/- 783 pg/mL [SEM], P = 0.001) and were also less responsive to LPS (4444 +/- 86 pg/mL [SEM] vs. 6666 +/- 91 pg/mL [SEM], P = 0.058). However, there was no difference in MAPK activation. In vivo HTS prevents excessive AM activation during systemic inflammation. This suppression is mediated through alternate pathways and does not induce the classic MAPK signaling cascade.
Staudenmayer
Kristan L
KL
Department of Surgery, University of Washington, Harborview Medical Center, Seattle, Washington, USA.
Maier
Ronald V
RV
Jelacic
Sandra
S
Bulger
Eileen M
EM
D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004789:Enzyme Activation; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D016207:Cytokines; D008070:Lipopolysaccharides; D012462:Saline Solution, Hypertonic; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D020928:Mitogen-Activated Protein Kinases