Endogenous versus exogenous glucocorticoid responses to experimental bacterial sepsis.
Although lack of adrenals dramatically reduces resistance against sepsis generally, the value of glucocorticoid levels above those normally produced by stress remains controversial. An early and long-held concept is that glucocorticoid protection against lipopolysaccharides in animal models is important. Supporting this concept, C3H/HeJ mice, lacking Toll-like receptor-4 (TLR-4), and consequently, endotoxin hyporesponsive, have recently been shown to be resistant to glucocorticoid protection against live Escherichia coli. Effective antibiotic intervention, as an additional parameter and with concomitant administration of glucocorticoid, not only allows for expected antibiotic protection but also for glucocorticoid protection against E. coli or Staphylococcus aureus of mice sensitized to tumor necrosis factor alpha, regardless of the status of the TLR-4 receptor. TLRs, including but not limited to TLR-2, may be involved in glucocorticoid protective efficacy against Gram-positive and Gram-negative sepsis. Overlapping and possibly endotoxin-independent signaling may become important considerations.
Silverstein
Richard
R
Department of Biochemistry, University of Kansas School of Medicine, Kansas City, USA. rsilvers@kumc.edu
Johnson
Donald C
DC
D000818:Animals; D016470:Bacteremia / Q000517:prevention & control*; D029721:Drosophila Proteins; D004927:Escherichia coli Infections / Q000517:prevention & control*; D005938:Glucocorticoids / Q000494:pharmacology* / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D011956:Receptors, Cell Surface / Q000502:physiology; D013203:Staphylococcal Infections / Q000517:prevention & control*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D005938:Glucocorticoids; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors