Context: Sepsis is a leading cause of death in the Western world and can be associated with failure of the hypothalamic-pituitary-adrenal axis. A coordinated response of the adrenal and immune system is of vital importance for survival during sepsis. Within the immune response, Toll-like receptors (TLRs) play a crucial role by recognising pathogen-associated molecules such as bacterial DNA. TLR-9 can detect motifs of unmethylated CpG dinucleotides (CpG-DNA) being present in bacterial DNA.

Objective: We investigated whether TLR-9 is expressed in human and murine adrenal glands and whether its activation is associated with an adrenal response.

Design: Human foetal and adults adrenal glands; wild-type, C57BL/6 and TLR-9 deficient, TLR-9^-/- mice; and in vitro cell line models.

Setting: University Hospital

Results: TLR-9 is expressed in human and murine adrenal glands as well as in in vitro cell lines (Y-1 and NCI-H295R cells). CpG-ODN challenge caused a three-fold increase in plasma levels of corticosterone in Wild-type mice. This effect was not observed in TLR-9^-/- mice. Furthermore, CpG-ODN challenge resulted in a strong release of several inflammatory cytokines, such as tumour necrosis factor- and interleukin-1, -6, -10 and -12 in vivo as well as in vitro. Again, this effect was not present in TLR-9^-/- mice.

Conclusions: TLR-9 is present in both murine and human adrenal glands. TLR-9 stimulation led to a corticosterone and inflammatory cytokine response. TLR-9 may play a role in the regulation of the hypothalamic-pituitary-adrenal axis during conditions where bacterial DNA is present.