HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 98/6/2155    most recent 01241.2004v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Haley, M. Articles by Eichacker, P. Q. Search for Related Content PubMed PubMed Citation Articles by Haley, M. Articles by Eichacker, P. Q.

Neutrophil inhibition with L-selectin-directed MAb improves or worsens survival dependent on the route but not severity of infection in a rat sepsis model

Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland

Submitted 4 November 2004 ; accepted in final form 26 January 2005

Both route and severity of infection may influence immunomodulator agents in sepsis. We studied the effect of each variable on HRL-3, an L-selectin-directed MAb that inhibits neutrophil function, in a rat sepsis model. Animals (n = 800) were randomized to be treated with either HRL-3 or placebo and to receive Escherichia coli either intravenously (IV) or intrabronchially (IB) in doses producing low or high mortality rates. Animals received antibiotics and were observed for 168 h. Route but not dose of E. coli altered the effects HRL-3 on mortality rate (mean hazards ratio ± SE). With IV E. coli, compared with control, HRL-3 was beneficial and reduced the hazards ratio both early (0 to 6 h; –0.75 ± 0.23) and late (6 to 168 h; –0.72 ± 0.36) (P = 0.001 and 0.04, respectively, over all E. coli doses). In contrast, with IB E. coli HRL-3 reduced the hazards ratio early (–1.1 ± 0.36) but worsened it late (0.87 ± 0.23) (P = 0.002 for both effects over all E. coli doses) in patterns significantly different from IV E. coli (P < 0.0001). Compared with control, although HRL-3 did not alter lung neutrophil numbers or injury score at 6 or 168 h with IV E. coli (P = ns for all), it reduced both early and increased them late with IB E. coli (P 0.05 for all comparing 6 with 168 h). Thus immunomodulators inhibiting neutrophil function, although potentially beneficial with sepsis due to intravascular infection, may be harmful with extravascular infection regardless of severity.

shock; adhesion; treatment

This article has been cited by other articles:

				A. Zarbock, M. Schmolke, T. Spieker, K. Jurk, H. Van Aken, and K. Singbartl Acute Uremia but Not Renal Inflammation Attenuates Aseptic Acute Lung Injury: A Critical Role for Uremic Neutrophils J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3124 - 3131. [Abstract] [Full Text] [PDF]