Biomechanical factors may be the main contributor to entheseal changes in normal adults

Pathophysiology and treatment of rheumatic disease

The role of Toll-like receptors in the immune-adrenal crosstalk

Sepsis and septic shock remain major health concerns worldwide, and rapid activation of adrenal steroid release is a key event in the organism's first line of defense during this form of severe illness. Toll-like receptors (TLRs) are critical in the early immune response upon bacterial infection, and recent data from our lab demonstrate a novel link between the innate immune system and the adrenal stress response mediated by TLRs. Glucocorticoids and TLRs regulate each other in a bidirectional way. Bacterial toxins acting through TLRs directly activate adrenocortical steroid release. TLR-2 and TLR-4 are expressed in human and mice adrenals and TLR-2 deficiency is associated with an impaired glucocorticoid response. Furthermore, TLR-2 deficiency in mice is associated with marked cellular alterations in adrenocortical tissue. TLR-2-deficient mice have an impaired adrenal corticosterone release following inflammatory stress induced by bacterial cell wall compounds. This defect appears to be associated with a decrease in systemic and intraadrenal cytokine expression. In conclusion, TLRs play a crucial role in the immune–adrenal crosstalk. This close functional relationship needs to be considered in the treatment of inflammatory diseases requiring an intact adrenal stress response.Fil: Bornstein, S. R.. Heinrich Heine University; AlemaniaFil: Ziegler, C. G.. Heinrich Heine University; AlemaniaFil: Krug, A. W.. Heinrich Heine University; AlemaniaFil: Kanczkowski, W.. Heinrich Heine University; AlemaniaFil: Besuhli, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: McCann, S. M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Wirth, M.. University of Dresden; AlemaniaFil: Zacharowski, K.. Heinrich Heine University; Alemani