title: Exogenous surfactant restores lung function but not peripheral immunosuppression in ventilated surfactant-deficient rats.
abstract: The authors have previously shown that mechanical ventilation can result in increased pulmonary inflammation and suppressed peripheral leukocyte function. In the present study the effect of surfactant therapy on pulmonary inflammation and peripheral immune function in ventilated surfactant-deficient rats was assessed. Surfactant deficiency was induced by repeated lung lavage, treated rats with surfactant or left them untreated, and ventilated the rats during 2 hours. Nonventilated rats served as healthy control group. Expression of macrophage inflammatory protein (MIP)-2 was measured in bronchoalveolar lavage (BAL), interleukin (IL)-1beta, and heat shock protein 70 (HSP70) were measured in total lung homogenates. Outside the lung phytohemagglutinin (PHA)-induced lymphocyte proliferation, interferon (IFN)-gamma and IL-10 production, and natural killer activity were measured in splenocytes. After 2 hours of mechanical ventilation, expression of MIP-2, IL-1beta, and HSP70 increased significantly in the lungs of surfactant-deficient rats. Outside the lung, mitogen-induced proliferation and production of IFN-gamma and IL-10 reduced significantly. Only natural killer cell activity remained unaffected. Surfactant treatment significantly improved lung function, but could not prevent increased pulmonary expression of MIP-2, IL-1beta, and HSP70 and decreased peripheral mitogen-induced lymphocyte proliferation and IFN-gamma and IL-10 production in vitro. In conclusion, 2 hours of mechanical ventilation resulted in increased lung inflammation and partial peripheral leukocyte suppression in surfactant-deficient rats. Surfactant therapy ameliorated lung function but could not prevent or restore peripheral immunosuppression. The authors postulate that peripheral immunosuppression may occur in ventilated surfactant deficient patients, which may enhance susceptibility for infections.
authors.affiliation: Pediatric Intensive Care Unit, and Laboratory for Psycho-Neuroimmunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Harriet A
authors.initials: HA
authors.lastname: Vreugdenhil
authors.forename: Burkhard
authors.initials: B
authors.lastname: Lachmann
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Haitsma
authors.forename: Jitske
authors.initials: J
authors.lastname: Zijlstra
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: Nicolaas J
authors.initials: NJ
authors.lastname: Jansen
authors.forename: Adrianus J
authors.initials: AJ
authors.lastname: van Vught
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002245:Carbon Dioxide / Q000097:blood; D002455:Cell Division / Q000276:immunology; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000378:metabolism; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008170:Lung Compliance; D010100:Oxygen / Q000097:blood; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology*; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D013154:Spleen / Q000166:cytology
chemical_list: D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D011663:Pulmonary Surfactants; D016753:Interleukin-10; D002245:Carbon Dioxide; D007371:Interferon-gamma; D010100:Oxygen