Bird; Royal Perth Hospital, Perth Crenolanib – S. Webb, J. Chamberlain, G. McEntaggart, A. Gould; Royal Prince Alfred Hospital, Sydney – R. Totaro, D. Rajbhandari; Sir Charles Gairdner Hospital, Nedlands – S. Baker, B. Roberts; St Andrew’s War Memorial Hospital, Brisbane – P. Lavercombe, R. Walker; St George Hospital, Sydney – J. Myburgh, V. Dhiacou; St Vincent’s Hospital, Melbourne – J. Santamaria, R Smith, J. Holmes; St Vincent’s, Sydney – P. Nair, C. Burns; Tauranga Hospital, Tauranga, New Zealand – T. Browne, J. Goodson; Waikato Hospital, Hamilton, New Zealand – F. van Haren, M. La Pine; Warringal Private, Heidelberg – G. Hart, J. Broadbent; Wellington Hospital, Wellington, New Zealand – P. Hicks, D. Mackle, L. Andrews; Western Hospital, Melbourne – C. French. H. Raunow, L.

Keen; and Wollongong Hospital, Wollongong – A. Davey-Quinn, F. Hill, R. Xu.
Toll-like receptors (TLRs) are known to play a crucial role in the innate immune response in mammals. TLRs are involved in the recognition of pathogenic molecules like lipopolysaccharide (LPS), lipoteichoic acid (LTA), bacterial DNA and others [1]. Furthermore, there is good evidence for the involvement of TLRs in the crosstalk of immune system and the hypothalamic-pituitary-adrenal (HPA) axis [2-5]. In TLR2 deficient mice, adrenal glands are significantly larger compared to wild-type mice. However, the corticosterone plasma levels are significantly lower in the deficient mice. Inducing a systemic inflammation with bacterial wall components in TLR2 deficient mice leads to an impaired release of both corticosterone and pro-inflammatory cytokines compared to wild-type animals [6].

A similar difference of physiology and pathophysiology of the HPA axis exists between wild-type and TLR4 deficient mice. Under physiological conditions the cortex of the adrenal glands is significantly enlarged and plasma concentrations of corticosterone and the pro-inflammatory cytokines tumor necrosis factor (TNF)-��, interleukin (IL)-1�� and IL-12 are significantly higher when compared to wild-type animals. Systemic inflammation induces an increase of corticosterone plasma concentration in wild-type, but a decrease in TLR4 deficient mice [7].In humans, single nucleotide polymorphisms (SNPs) are described. For TLR2 the most investigated SNP is Arg753Gln which is located in the coding region with a prevalence of approximately 3 to 9.

4% in the Caucasian population [8-13]. Children carrying the SNP of Arg753Gln are more susceptible to febrile infections compared to non-carriers [13]. Furthermore, the Arg753Gln polymorphism has been reported to increase the risk of gram-positive and candida sepsis in critical ill patients [8,10], and to increase restenosis rate in patients Brefeldin_A who underwent percutaneous transluminal coronary angioplasty [14].The two most investigated SNPs of TLR4 are Asp299Gly and Thr399Ile. Six to 14% of the European population are double heterozygote carriers, whereas less than 0.