Proinflammatory cytokines increase in sepsis after anti-adhesion molecule therapy

• Published in: Shock (Augusta, Ga.) Vol. 13; no. 5; p. 404
• Main Authors: Welty-Wolf, K E, Carraway, M S, Ghio, A, Kantrow, S P, Huang, Y C, Piantadosi, C A
• Format: Journal Article
• Language: English
• Published: United States 01.05.2000
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Antigens, CD - blood; Cytokines - blood; E-Selectin - immunology; Escherichia coli - immunology; Escherichia coli - pathogenicity; Escherichia coli Infections - immunology; Escherichia coli Infections - therapy; Inflammation Mediators - blood; Intercellular Adhesion Molecule-1 - immunology; Interleukin-1 - blood; Interleukin-6 - blood; Interleukin-8 - blood; L-Selectin - immunology; Male; Papio; Receptors, Tumor Necrosis Factor - blood; Receptors, Tumor Necrosis Factor, Type I; Sepsis - immunology; Sepsis - therapy
• ISSN: 1073-2322
• DOI: 10.1097/00024382-200005000-00010

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.