engleski

Monocyte response to LPS after exposure to corticosteroids and chloroquine with implications for systemic lupus erythematosus

Essential part of response to infection is early pathogen recognition and adequate innitiation of innate immunity. To investigate whether less aggressive immunomodulatory treatment may still affect recognition and response to Gram-negative bacteria, we measured TLR4 expression in monocytes of untreated systemic lupus erythematosus patients on chloroquine and low-dose steroid therapy, and examined the drugs' influence on monocyte TLR4 expression in peripheral blood mononuclear cell (PBMC)culture. Additionally, we deteremined whether induction of monocyte NF-kB signaling, TNF-alfa and IL-6 production with lipopolysaccharide (LPS), a TLR4 ligand, can be altered with dexamethasone, chloroquine or both. There was no statistically significant difference in TLR4 expression between SLE patients and controls, even though treated SLE patients tended to have lower frequency of TLR4 monocytes and TLR4 mean fluorescence intensity than healthy controls. However, neither dexamethasone nor chloroquine had major influence on TLR4 expression in vitro or supressed LPS-induced NF-kB activation in monocytes, although dexamethasone decreased TNF-alfa and IL-6 production. Therefore, even if low-dose steroids or chloroquine do not seem to affect TLR4 expression and signaling, steroids might decrease cyokine production in response to LPS.

toll-like receptor 4; systemic lupus erythematosus; monocytes; NF-kB; chloroquine; dexamethasone

nije evidentirano