Translocated LPS might cause endotoxin tolerance in circulating monocytes of cystic fibrosis patients.
Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from abnormalities in the gene codes of a chloride channel. The lungs of CF patients are chronically infected by several pathogens but bacteraemia have rarely been reported in this pathology. Besides that, circulating monocytes in CF patients exhibit a patent Endotoxin Tolerance (ET) state since they show a significant reduction of the inflammatory response to bacterial stimulus. Despite a previous description of this phenomenon, the direct cause of ET in CF patients remains unknown. In this study we have researched the possible role of microbial/endotoxin translocation from a localized infection to the bloodstream as a potential cause of ET induction in CF patients. Plasma analysis of fourteen CF patients revealed high levels of LPS compared to healthy volunteers and patients who suffer from Chronic Obstructive Pulmonary Disease. Experiments in vitro showed that endotoxin concentrations found in plasma of CF patients were enough to induce an ET phenotype in monocytes from healthy controls. In agreement with clinical data, we failed to detect bacterial DNA in CF plasma. Our results suggest that soluble endotoxin present in bloodstream of CF patients causes endotoxin tolerance in their circulating monocytes.
Servicio de Microbiología and CIBER en Epidemiología y Salud Pública (CIBERESP), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain.
Rosa
R
del Campo
Eriel
E
Martínez
Carlos
C
del Fresno
Raquel
R
Alenda
Vanesa
V
Gómez-Piña
Irene
I
Fernández-Ruíz
María
M
Siliceo
Teresa
T
Jurado
Victor
V
Toledano
Francisco
F
Arnalich
Francisco
F
García-Río
Eduardo
E
López-Collazo
D001483:Base Sequence; D001692:Biological Transport; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000097:blood*; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D004731:Endotoxins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects*
D017931:DNA Primers; D004731:Endotoxins; D008070:Lipopolysaccharides