Effect of CD14 blockade in rabbits with Escherichia coli pneumonia and sepsis.
CD14, a pattern recognition receptor found on myeloid cells, is a critical component of the innate immune system that mediates local and systemic host responses to Gram-negative and Gram-positive bacterial products. Previous studies in normal animals have tested the effect of CD14 blockade on the systemic response to i.v. LPS. The goals of the study were to determine whether CD14 blockade protected against the deleterious systemic response associated with Escherichia coli pneumonia and to determine whether this strategy affected the pulmonary response to tissue infection. Rabbits were pretreated with either anti-CD14 mAb or isotype control mAb at 2.5 mg/kg. E. coli (1 x 109 CFU) was inoculated into the lungs, and the animals were observed for either 4 or 24 h. The blockade of CD14 improved the mean arterial blood pressure (p = 0.001) and decreased the i.v. fluid requirements (p = 0.01). Although this therapy protected the vascular compartment, rabbits treated with anti-CD14 mAb had increased bacterial burdens in the bronchoalveolar lavage fluid recovered from the instilled lung (p = 0.005) and widened alveolar-arterial oxygen difference. Blockade of CD14 prevents the deleterious systemic responses that occur in sepsis; however, other measures are necessary to control bacterial proliferation at the primary site of infection.
Frevert
C W
CW
Medical Research Service of the Seattle Department of Veterans' Affairs Medical Center, Division of Pulmonary/Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98101, USA. cfrevert@u.washington.edu
Matute-Bello
G
G
Skerrett
S J
SJ
Goodman
R B
RB
Kajikawa
O
O
Sittipunt
C
C
Martin
T R
TR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001794:Blood Pressure / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology / Q000382:microbiology; D018932:Chemokine CCL2 / Q000032:analysis; D002630:Chemotactic Factors / Q000032:analysis; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D006133:Growth Substances / Q000032:analysis; D007249:Inflammation / Q000276:immunology; D016209:Interleukin-8 / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D011659:Pulmonary Gas Exchange / Q000276:immunology; D011817:Rabbits; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D006133:Growth Substances; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha