PMID- 8328833
OWN - NLM
STAT- MEDLINE
DCOM- 19930809
LR  - 20190514
IS  - 0003-4932 (Print)
IS  - 1528-1140 (Electronic)
IS  - 0003-4932 (Linking)
VI  - 218
IP  - 1
DP  - 1993 Jul
TI  - Comparison of peripheral blood leukocyte kinetics after live Escherichia coli, 
      endotoxin, or interleukin-1 alpha administration. Studies using a novel 
      interleukin-1 receptor antagonist.
PG  - 79-90
AB  - OBJECTIVE: This study was undertaken to evaluate whether hematologic and 
      immunologic effects observed after bacteremia and endotoxemia in the host could 
      be replicated by administration of recombinant human interleukin-1 alpha (IL-1 
      alpha) in a primate model. Furthermore, to determine whether endogenously 
      produced interleukin-1 (IL-1) contributes to the changes observed during 
      endotoxemia or gram-negative septic shock, a specific IL-1 receptor antagonist 
      (IL-1 ra) was administered. SUMMARY BACKGROUND DATA: The lipopolysaccharide (LPS) 
      component of the outer membrane of gram-negative bacteria initiates a 
      constellation of metabolic and immunologic host responses. IL-1, a 
      macrophage-derived cytokine, acts as a key mediator in the host response to 
      infection and inflammation. METHODS: Baboons were randomly assigned to receive 
      either recombinant human IL-1 alpha, LPS, or live Escherichia coli both with or 
      without concomitant administration of IL-1ra. Blood was collected hourly and 
      analyzed using flow cytometric techniques. RESULTS: Both endotoxemia and live E. 
      coli bacteremia induced an acute granulocytopenia; however, the granulocytopenia 
      gradually resolved in the endotoxemic group, but was sustained in the bacteremic 
      group. An early lymphopenia and monocytopenia was elicited by LPS or E. coli and 
      persisted throughout the experiment. Recombinant human IL-1 alpha induced the 
      following: (1) an early, transient decline in granulocytes followed by a 
      sustained granulocytosis; (2) a lymphopenia; and (3) a transient monocytopenia 
      followed by a gradual return to baseline. Although IL-1ra had no effect on 
      leukocyte kinetics with either live E. coli or LPS, the IL-1ra significantly 
      abrogated the monocytopenia seen with recombinant human IL-1 alpha administration 
      alone. CONCLUSIONS: These results suggest that administration of recombinant 
      human IL-1 alpha can replicate some of the characteristic patterns of hematologic 
      change associated with bacteremia and endotoxemia. However, an endogenous IL-1 
      response is not required for these changes to occur. Rather, the data suggest 
      that other inflammatory mediators induced by endotoxemia or gram-negative 
      bacteremia, such as tumor necrosis factor-alpha (TNF alpha), may be involved.
FAU - Hawes, A S
AU  - Hawes AS
AD  - Department of Surgery, Cornell University Medical College, New York, New York.
FAU - Fischer, E
AU  - Fischer E
FAU - Marano, M A
AU  - Marano MA
FAU - Van Zee, K J
AU  - Van Zee KJ
FAU - Rock, C S
AU  - Rock CS
FAU - Lowry, S F
AU  - Lowry SF
FAU - Calvano, S E
AU  - Calvano SE
FAU - Moldawer, L L
AU  - Moldawer LL
LA  - eng
GR  - CA 52108/CA/NCI NIH HHS/United States
GR  - GM 34695/GM/NIGMS NIH HHS/United States
GR  - GM 40586/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Ann Surg
JT  - Annals of surgery
JID - 0372354
RN  - 0 (Endotoxins)
RN  - 0 (IL1RN protein, human)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Sialoglycoproteins)
SB  - IM
MH  - Animals
MH  - Bacteremia/blood/immunology
MH  - Cell Division
MH  - Endotoxins/administration & dosage/*immunology
MH  - Escherichia coli/*immunology
MH  - Female
MH  - Granulocytes/cytology/immunology
MH  - Interleukin 1 Receptor Antagonist Protein
MH  - Interleukin-1/administration & dosage/*immunology
MH  - Kinetics
MH  - Leukocytes/cytology/*immunology
MH  - Lipopolysaccharides/administration & dosage/*immunology
MH  - Male
MH  - Monocytes/cytology/immunology
MH  - Papio
MH  - Random Allocation
MH  - Sialoglycoproteins/immunology
MH  - Toxemia/blood/immunology
PMC - PMC1242904
EDAT- 1993/07/01 00:00
MHDA- 1993/07/01 00:01
PMCR- 1993/07/01
CRDT- 1993/07/01 00:00
PHST- 1993/07/01 00:00 [pubmed]
PHST- 1993/07/01 00:01 [medline]
PHST- 1993/07/01 00:00 [entrez]
PHST- 1993/07/01 00:00 [pmc-release]
AID - 10.1097/00000658-199307000-00013 [doi]
PST - ppublish
SO  - Ann Surg. 1993 Jul;218(1):79-90. doi: 10.1097/00000658-199307000-00013.