Endothelial cells are main producers of interleukin 8 through toll-like receptor 2 and 4 signaling during bacterial infection in leukopenic cancer patients

CSMO Nijhuis, E Vellenga, SMGJ Daenen, WA Kamps, ESJM de Bont*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

31 Citaten (Scopus)

Samenvatting

Cancer patients who are leukopenic due to chemotherapy are susceptible to bacterial infections. Normally, clinical conditions during bacterial infections are caused by pathogen-associated molecular patterns, which are components that bind to Toll-like receptor (TLR) 2 (TLR-2) and TLR-4 on leukocytes, resulting in the production of inflammatory cytokines. The mechanism of this inflammatory response in cancer patients with diminished numbers of leukocytes is not completely clear. The levels of interleukin 1beta (IL-1beta) and tumor necrosis factor alpha measured in the circulation of leukopenic cancer patients are lower than those measured in that of nonleukopenic patients during bacterial infections, whereas plasma interleukin 8 (IL-8) levels show distinct identical increases during bacterial infections in both leukopenic and nonleukopenic patients. Normally, these cytokines are mainly secreted by leukocytes. In cancer patients with bacterial infections and a diminished number of leukocytes, other sources of IL-8 production, such as endothelial cells, might be expected. Endothelial cells instead of leukocytes become the most important producers of IL-8 during bacterial infections in patients with chemotherapy-induced leukopenia through TLR-2 and TLR-4 signaling. Whole blood samples from six cancer patients were stimulated with lipopolysaccharide (LPS), and then IL-8 concentrations in supernatants were measured. Further, human umbilical vein endothelial cells (HUVECs) were incubated with sera from leukopenic cancer patients with or without bacterial infections, and then IL-8 concentrations in supernatants were measured (n = 6). In addition, the same HUVEC experiment was performed with the addition of neutralizing antibodies against TLR-2 and TLR-4. During leukopenia (

Originele taal-2English
Pagina's (van-tot)558-563
Aantal pagina's6
TijdschriftClinical and Diagnostic Laboratory Immunology
Volume10
Nummer van het tijdschrift4
DOI's
StatusPublished - jul-2003

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