Intratracheal administration of endotoxin and cytokines. VI. Antiserum to CINC inhibits acute inflammation.
Cytokine-induced neutrophil chemoattractant (CINC), a chemotactic molecule of the interleukin (IL)-8 family, is known to be induced in the rat in response to tumor necrosis factor (TNF), IL-1, and lipopolysaccharide (LPS). Intratracheal injection of endotoxin (LPS) is shown to cause CINC mRNA expression in pulmonary tissue, peaking after 2 h, and CINC protein expression in bronchoalveolar lavage (BAL) fluid, peaking after 2-4 h. Intratracheal injection of synthetic CINC causes acute inflammation that is abrogated by coinjection of antiserum to purified natural rat CINC. Intratracheal injection of antiserum to CINC inhibits intratracheal LPS- and IL-1-induced neutrophil emigration into BAL fluid by approximately 60-70%. Despite the anti-inflammatory activity of anti-CINC antiserum, TNF is elevated in the lavage fluid of rats receiving anti-CINC, suggesting that CINC may act in a negative feedback loop to downregulate TNF expression. Intratracheal injection of antiserum to CINC combined with intravenous injection of anti-E-selectin antibody inhibits intratracheal LPS- and IL-1-induced neutrophil emigration into BAL fluid by approximately 75-85%. CINC-mediated chemotactic activity and E-selectin-mediated adherence of neutrophils to endothelium contribute significantly to the pathogenesis of LPS-initiated acute inflammation.
Ulich
T R
TR
Department of Pathology, University of California San Diego School of Medicine 92103.
Howard
S C
SC
Remick
D G
DG
Wittwer
A
A
Yi
E S
ES
Yin
S
S
Guo
K
K
Welply
J K
JK
Williams
J H
JH
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000008:administration & dosage* / Q000494:pharmacology; D019040:E-Selectin; D004731:Endotoxins / Q000008:administration & dosage* / Q000494:pharmacology; D006133:Growth Substances / Q000235:genetics / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology*; D007267:Injections; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011014:Pneumonia / Q000139:chemically induced / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D016207:Cytokines; D019040:E-Selectin; D004731:Endotoxins; D006133:Growth Substances; D007106:Immune Sera; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha