Novel pathways for glucocorticoid effects on neutrophils in chronic inflammation

Abstract

Neutrophils have been implicated in mediating much of the tissue damage associated with chronic inflammatory diseases such as rheumatoid arthritis, where they are involved in destruction of both cartilage and bone. Glucocorticoids are powerful anti-inflammatory agents, often used in the treatment of this autoimmune disease. They exert significant inhibitory effects on neutrophil activation and functions, such as chemotaxis, adhesion, transmigration, apoptosis, oxidative burst, and phagocytosis. The mechanisms by which glucocorticoids exert these effects on neutrophils are unclear. Evidence from studies of inflammation in human subjects and animal models suggests that annexin-I an endogenous, glucocorticoid-induced protein also known as lipocortin-1, has a pivotal role in modulating neutrophil activation, transmigratory, and phagocytic functions. Furthermore, we present evidence for altered neutrophil functions in rheumatoid arthritis that correspond to a significantly reduced capacity of these cells to bind annexin-I. A proposed novel pathway for glucocorticoid actions on neutrophils involving annexin-I could explain the development of chronic neutrophil activation in diseases such as rheumatoid arthritis.

Acute Effects of Dihydrocapsaicin and Capsaicin on the Distribution of White Blood Cells in Rats

“…On the other hand, glucocorticoid (corticosterone) is known to induce the mobilization of neutrophils from the bone marrow into the circulating blood ( 24 ), inhibit apoptosis of circulating neutrophils ( 25 ) and suppress the inflammatory consequences of neutrophil migration and activation ( 26 ). In the present study, however, serum corticosterone concentrations in the DHC and CAP groups at 3 h did not change significantly as compared with the CON group.…”

Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function

“…Using this methodology, we found that mature marrow granulocytes (band cells, segmented cells) were able to adequately carry out phagocytosis, produce superoxide, and respond to chemotactic factors subsequent to the Gc exposure. This is in marked contrast to many previous studies where exposure of peripheral neutrophils to pharmacological steroids was shown to alter their function (17). To carry out these studies, CS was delivered to mice continuously via tablet implant to mimic chronic stress events.…”

An overview of the effects of annexin 1 on cells involved in the inflammatory process

“…Use of more stable, short N-terminal derived peptides has helped overcome this problem. Indeed, peptide Ac2-26 inhibited phagocytosis of immune complexes (Goulding et al 1998) as well as superoxide generation (Euzger et al 1999) by human monocytes.…”