Hypertonic resuscitation of hemorrhagic shock upregulates the anti-inflammatory response by alveolar macrophages.
BACKGROUND
Resuscitated hemorrhagic shock predisposes patients to the development of acute respiratory distress syndrome (ARDS). Hypertonic saline (HTS) has been shown to inhibit immune cell activation in response to lipopolysaccharide (LPS) in vitro and to reduce lung damage when used for resuscitation of hemorrhagic shock in vivo. We hypothesize that HTS resuscitation of hemorrhagic shock may exert this anti-inflammatory effect by modulating alveolar macrophage function leading to an altered balance between the proinflammatory and the counter-inflammatory response.


METHODS
A 2-hit rat model of shock resuscitation was used. Alveolar macrophages were harvested by bronchoalveolar lavage (BAL), and tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 were quantified in the cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Alternatively, 1 hour after resuscitation, animals received endotracheal LPS followed by endotracheal anti-IL-10 neutralizing antibody. Lung injury was determined by measuring BAL neutrophil counts 4 hours after LPS in vivo administration.


RESULTS
Systemic administration of HTS significantly modulates the responsiveness of alveolar macrophages. Specifically, HTS resuscitation inhibited LPS-induced TNF-alpha production while enhancing IL-10 release in response to LPS administered ex vivo and in vivo. Anti-IL-10 antibody in vivo partially reversed the lung protective effect of HTS resuscitation.


CONCLUSIONS
HTS resuscitation exerts an immunomodulatory effect on alveolar macrophages by shifting the balance of pro- and counter-inflammatory cytokine production in favor of an anti-inflammatory response. The in vivo data suggest a causal role for HTS-induced augmented IL-10 as protective. These findings suggest a novel mechanism for the in vivo salutary effect of HTS resuscitation on lung injury after resuscitated hemorrhagic shock.
Powers
Kinga A
KA
Department of Surgery, University of Toronto, University Health Network, Toronto General Hospital, Toronto, Canada.
Woo
James
J
Khadaroo
Rachel G
RG
Papia
Giuseppe
G
Kapus
Andras
A
Rotstein
Ori D
OD
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019610:Cytoprotection; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D011014:Pneumonia / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome; D012151:Resuscitation; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000906:Antibodies; D008070:Lipopolysaccharides; D012462:Saline Solution, Hypertonic; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10