Interleukins glucocorticoid inhibition

Knudsen PJ, Dinarello CA, Strom TB. Glucocorticoids inhibit transcriptional and post-transcriptional expression of interleukin 1 in U937 cells. J Immunol 1987 139 4129-4134. 

Ito, K., Barnes, P.J. and Adcock, I.M. (2000) Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-lbeta-induced histone H4 acetylation on lysines 8 and 12. Molecular and Cellular Biology, 20, 6891-6903. 

In addition to direct effects on genes regulating inflammation, glucocorticoids also inhibit the transcription factors that initiate synthesis of pro-inflammatory cytokines (e.g., interleukin-1, tumor necrosis factor), enzymes (e.g., COX-2, nitric oxide synthase), and receptor proteins (e.g., natural killer receptors).17,87,89 Glucocorticoids may also exert some of their effects via a membrane-bound receptor that regulates activity of macrophages, eosinophils, T lymphocytes, and several other types of cells involved in the inflammatory response.89 Consequently, glucocorticoids affect many aspects of inflammation, and their powerful anti-inflammatory effects in rheumatoid arthritis result from their ability to blunt various cellular and chemical components of the inflammatory response. 

Ciclosporin and related substances inhibit the production of cytokines, in particular interleukin-2. In contrast to glucocorticoids, the plethora of accompanying metabolic effects is absent (see p.306 for more details). 

NITRERGIC STIMULANTS mimic, or cause the production and release of nitric oxide (NO), which is an important mediator that is synthesized on demand. The actions of nitric oxide are very widespread, and imbalance is likely to be involved in a number of disease states. Nitric oxide synthase (NOS) has a widespread distribution in the body, and isoforms are recognized specifically constitutive and inducible (iNOS) forms. Both forms are cytosolic, Ca /calmodulin and NADPH-dependent, and inhibited by L-arginine derivatives. Induction of iNOS is by various inflammatory cytokines, particularly those stimulated by bacterial lipopolysaccarides, including tumour necrosis factor a. interferon 7 and interleukin 1 p. Induction of iNOS only is inhibited by GLUCOCORTICOIDS. 

Lee SW, Tsou AP, Chan H, et al. Glucocorticoids selectively inhibit the transcription of the interleukin ip gene and decrease the stability of interleukin ip mRNA. Immunology 1988 85 1204-1208. 

Epinephrine and isoproterenol (via cAMP mechanisms) and theophylline (via cAMP or block of adenosine receptors) inhibit the release of mediators from mast cells and basophils and cause bronchodilation. Diphenhydramine competitively blocks histamine actions at H, receptors, actions that would otherwise cause bronchoconstriction and increased capillary permeability. Dexamethasone has multiple cellular effects, including inhibition of IgE-producing clone proliferation, block of T helper cell function, and anti-inflammatory actions. Most of the actions of glucocorticoids result from decreases in the synthesis of cytokines (eg, interleukins, platelet activating factor) or eicosanoids (leukotrienes, prostaglandins). 

Glucocorticoids depress monocyte/macrophage fund ion and decrease circulating thymus-derived lymphocytes (T-cclis), especially helper Tj lymphocyte.s. The release of interleukins lL-1 and lL-2 (necessaty to activate and. stimulate iymphantigenic stimulation and the prrxluc-vion of antibody are also inhibited. 

---