TY - JOUR
T1 - Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E. coli pneumonia in rats
AU - Freeman, Bradley D.
AU - Correa, Rosaly
AU - Karzai, Waheedulla
AU - Natanson, Charles
AU - Patterson, Mary
AU - Banks, Steve
AU - Fitz, Yvonne
AU - Danner, Robert L.
AU - Wilson, Laura
AU - Eichacker, Peter Q.
PY - 1996/6
Y1 - 1996/6
N2 - We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FI(O2)) values studied (FI(O2) = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FI(O2) = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAB 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 - 1.20 and 2.39 - 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 - 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 - 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.
AB - We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FI(O2)) values studied (FI(O2) = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FI(O2) = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAB 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 - 1.20 and 2.39 - 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 - 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 - 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.
KW - CD11b/CD18
KW - Escherichia coli
KW - monoclonal antibody 1b6
KW - oxygen toxicity
KW - recombinant granulocyte colony- stimulating factor
UR - http://www.scopus.com/inward/record.url?scp=8944251133&partnerID=8YFLogxK
U2 - 10.1152/jappl.1996.80.6.2066
DO - 10.1152/jappl.1996.80.6.2066
M3 - Article
C2 - 8806915
AN - SCOPUS:8944251133
SN - 8750-7587
VL - 80
SP - 2066
EP - 2076
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 6
ER -