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

Essential part of a response to infection is early pathogen recognition and adequate initiation of innate immunity. One of the hallmarks of systemic lupus erythematosus (SLE) is reduced resistance to infection despite overall hyperactivity of the immune system. Immunosuppressive drugs (high-dose corticosteroids and cytotoxic agents) are independent risk factors for infection in SLE, with bacteria as predominant cause. 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 SLE patients and 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 determined whether induction of monocyte NF-κB signalling, TNF-α 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 patients with SLE 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 suppressed LPS-induced NF-κB activation in monocytes, although dexamethasone decreased TNF-α and IL-6 production. Therefore, even if low-dose steroids or chloroquine do not seem to affect TLR4 expression and signalling, steroids might decrease cytokine production in response to LPS.