Effect of anti-CD14 monoclonal antibody on clearance of Escherichia coli bacteremia and endotoxemia

Abstract

Anti-CD14 monoclonal antibody has the capacity to interfere with the innate immune response and systemic microbial clearance in experimental animals with E. coli bacteremia. The concomitant administration of effective antimicrobial therapy eliminated differences in the rate of microbial clearance between the control antibody and the CD14 monoclonal antibody. These results indicate that care should be taken in clinical trials with anti-CD14 monoclonal antibodies to ensure that adequate antimicrobial therapy is administered in the presence of systemic bacterial infection.

A Nonsynonymous Polymorphism of IRAK4 Associated with Increased Prevalence of Gram-Positive Infection and Decreased Response to Toll-Like Receptor Ligands

“…This amino acid substitution may disrupt IRAK4 signaling and result in a less-effective immune response to invading pathogens so that critically ill patients carrying the C/T/A clade have an increased risk of positive bacterial cultures. Our finding that the C/T/A haplotype clade of IRAK4 is associated with increased prevalence of positive bacterial cultures at admission to the ICU is consistent with our previous studies [36] , and with recent animal studies [37][38][39] which suggest that polymorphisms of innate immunity genes could be associated with impaired clearance of bacteria. A number of studies have shown that rare germline mutations in IRAK4 cause recurring bacterial infections in children and deficiencies in cytokine production in response to a range of microbial-derived TLR agonists and to recombinant IL-1 ␤ or IL-18 [10-13, 40, 41] .…”

Lipopolysaccharide Binding Protein Is an Essential Component of the Innate Immune Response toEscherichia coliPeritonitis in Mice

“…administration of live E. coli O111:B4 in vivo (5,13). In addition, anti-CD14 antibodies did not impair the outcome in E. coli O111:B4-infected mice but decreased bacterial clearance in E. coli O18:K1-challenged rabbits (13,18). Moreover, C3H/HeJ mice, which are not responsive to LPS due to a point mutation in the tlr4 gene, are highly susceptible to E. coli O18:K1 infection but not to E. coli O111:B4 infection (4, 7).…”

CD14 Impairs Host Defense against Gram‐Negative Sepsis Caused byBurkholderia pseudomalleiin Mice

“…Furthermore, CD14 has been found to play a key role in mounting an adequate innate immune response during gram-negative bacterial infection [21]. Indeed, in in vivo models of infection, inhibition or elimination of CD14 resulted in an increased outgrowth of different gramnegative bacterial species [20,[22][23][24][25]. We have previously documented a clear role for CD14 in improving the pulmonary clearance of clinically relevant gram-negative respiratory pathogens such as Haemophilus influenzae and Acinetobacter baumannii [24,25].…”