Glucocorticoid resistance in inflammatory diseases | Arthritis Information
Glucocorticoid resistance or insensitivity is a major barrier to the treatment of several common inflammatory diseases—including chronic obstructive pulmonary disease and acute respiratory distress syndrome; it is also an issue for some patients with asthma, rheumatoid arthritis, and inflammatory bowel disease. Several molecular mechanisms of glucocorticoid resistance have now been identified, including activation of mitogen-activated protein (MAP) kinase pathways by certain cytokines, excessive activation of the transcription factor activator protein 1, reduced histone deacetylase-2 (HDAC2) expression, raised macrophage migration inhibitory factor, and increased P-glycoprotein-mediated drug efflux. Patients with glucocorticoid resistance can be treated with alternative broad-spectrum anti-inflammatory treatments, such as calcineurin inhibitors and other immunomodulators, or novel anti-inflammatory treatments, such as inhibitors of phosphodiesterase 4 or nuclear factor κB, although these drugs are all likely to have major side-effects. An alternative treatment strategy is to reverse glucocorticoid resistance by blocking its underlying mechanisms. Some examples of this approach are inhibition of p38 MAP kinase, use of vitamin D to restore interleukin-10 response, activation of HDAC2 expression by use of theophylline, antioxidants, or phosphoinositide-3-kinase-δ inhibitors, and inhibition of macrophage migration inhibitory factor and P-glycoprotein.
There is that Vit. D connection again! Interesting!
I have always felt that Vitamin D plays a big role in AI diseases, at least it has for me. While I haven't yet read the linked article I must say this....holy cow! I had a suspicion that my RA was somehow becoming resistant to prednisone due to the high dosages that have had to be used to get a response. I guess now I know why the 40mg that would normally give me no swelling, inflammation, or pain isn't doing much at all for me now.
[QUOTE=waddie]There is that Vit. D connection again! Interesting!
[/QUOTE]
Rather off-topic...I read an interesting article in some magazine in some waiting room recently (sorry for not having the details at hand), wherein vitamin D insufficiency was associated with bacterial vaginosis and its accompanying host of pregnancy and birth-related misadventures.
As bacterial vaginosis can be secondary problem in autoimmune diseases it seems reasonable, at least to me, to suspect that vitD could play a role in both prevention and treatment.
A quick internet search brings up many sites featuring articles on the subject from the past couple of weeks such as this one:
http://www.medscape.com/viewarticle/703577Quote from link: "A better understanding of the vitamin D-BV relation will be
ascertained with prospective studies of 'incident' BV infections,
persistent infections, and infections that spontaneously resolve," the
study authors conclude. "It is also of considerable importance to
explore the effect of maternal vitamin D on particular organisms or
flora patterns other than BV that are linked to adverse outcomes. If
our results are replicated in other studies, vitamin D deficiency may
contribute to the racial disparity in the prevalence of BV and other
adverse outcomes of pregnancy."
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