Glucocorticoid induced apoptosis

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T-cell activity, thereby terminating the inflammation of the central nervous system [75]. Moreover, corticoids may reduce allergen specific T-cells through apoptosis, which is one of the mechanisms of effectiveness of corticoids in asthmatics [76], as well as induce apoptosis of endomysial T-cells in human idiopathic polymyositis, thus modifying the inflammation [77]. Interestingly, the expression of Bcl-2 may be an important factor in protecting the lymphocytes in inflamed synovial membranes from glucocorticoid-induced apoptosis [78]. 

Radu CG, Cheng D, Nijagal A et al (2006) Normal immune development and glucocorticoid-induced thymocyte apoptosis in mice deficient for the T-cell death-associated gene 8 receptor. Mol Cell Biol 26 668-677... 

Fuchs, B.A., and Pruett, S.B., Morphine induces apoptosis in murine thymocytes in vivo but not in vitro Involvement of both opiate and glucocorticoid receptors, J. Pharmacol. Exp. Ther., 266, 417, 1993. 

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Intracellular mechanisms governing apoptosis are as yet poorly understood. However, there are indications that internal controls in granulocytes may differ from lymphoid cells. In thymocytes, elevation of intracellular calcium concentration ([Ca " ] ) by calcium ionophores induces apoptosis, and apoptosis induced by other stimuli, such as glucocorticoids, is associated with rises in [Ca " ] (McConkey et al., 1989). However, in neutrophils spontaneously undergoing apoptosis, there were no such rises in [Ca " ] , and agents increasing [Ca " ] caused dramatic slowing of neutrophil apoptosis without... 

Upon SAg challenge in vivo, there is massive proliferation of the activated T cells and the number of V(3-specific T cells increases dramatically. Later on, their number is reduced due to activation-induced apoptosis. This process involves the typical DNA fragmentation, and affects preferentially V(3-specific CD4+ T cells [72], Stimulation with specific antigen and proinflammatory mediators, such as lipopolysaccharide, rescues T cells from death and promotes survival of SAg-stimulated T cells [80, 81]. The mechanism that triggers T cell apoptosis after SAg challenge is not well understood, but several events can contribute to it impaired IL-2 production, massive glucocorticoid release... 

The glucocorticoids have been found not only to increase apoptosis, but also to modulate the expression of apoptosis-related markers in both unstimulated and IL-2-stimulated T lymphocytes. In one study, this class of drugs induced apoptosis while reducing Bcl-2, Fas, and CD25 expression. Only negligible effects were detected on Bax expression, a fact which points towards a potential mechanism by which some corticoids exert their anti-inflammatory effects [59]. 

Glucocorticoids repress the expression and release of numerous cytokines in macrophages, thymocytes, and CD4+ splenocytes in addition, a protein-protein interaction with transcription factors such as NF-kB is involved in their anti-inflammatory activity. The only defect of immune suppression brought about by this class of drugs detected so far concerns the induced apoptosis of thymocytes and T lymphocytes [80]. 

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