Proinflammatory cytokines increase in sepsis after anti-adhesion molecule therapy.
Cytokine mediators and leukocyte-endothelial cell adhesion molecules are critical and interdependent components of the acute inflammatory response in sepsis. We hypothesized that the administration of monoclonal antibodies to intercellular adhesion molecule-1 (CD54) or E- and L-selectin (CD62E/L) would decrease serum levels of the proinflammatory cytokines interleukin-1beta (IL-1), IL-6, and IL-8 and tumor necrosis factor receptor (TNFR-1) in baboons during sepsis. Adult male baboons received infusions of 1 x 10(9) colony forming units (CFU)/kg heat-killed Escherichia coli (E. coli) followed 12 h later by live E. coli (1 x 10(10) CFU/kg). At the time of live bacterial infusion, six septic animals were treated with a monoclonal antibody to CD54 and six with an antibody to CD62E and L (1 mg/kg). Eight untreated septic animals served as controls. Sequentially drawn serum samples were assayed for IL-1, IL-6, IL-8, and TNFR-1 using enzyme-linked immunoassay (ELISA). Data were compared using Mann-Whitney U tests and Chi-square analyses. Median survival was decreased in both treatment groups compared to controls (P < 0.05). Peak IL-1 level was higher than controls in septic animals treated with anti-CD54 but not anti-CD62E/L (P < 0.05, P = NS, respectively). Elevations in IL-6, IL-8, and TNFR-1 were increased and prolonged in both antibody treated groups compared to controls (P < 0.05). These results provide the first in vivo evidence that leukocyte-endothelial adhesion molecules CD54 and CD62E/L regulate cytokine production in sepsis.
Welty-Wolf
K E
KE
Department of Medicine, Durham VA Medical Center, North Carolina 27710, USA.
Carraway
M S
MS
Ghio
A
A
Kantrow
S P
SP
Huang
Y C
YC
Piantadosi
C A
CA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000097:blood; D016207:Cytokines / Q000097:blood*; D019040:E-Selectin / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology / Q000628:therapy; D018836:Inflammation Mediators / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D019041:L-Selectin / Q000276:immunology*; D008297:Male; D010215:Papio; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D018805:Sepsis / Q000276:immunology* / Q000628:therapy*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D019040:E-Selectin; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin