My name is Carlo Riccardi.
I am a Professor of Pharmacology at the University of Perugia.
As shown in the first slide,
I will tell you about "Glucocorticoids Treatment in Allergic Diseases".
Glucocorticoids also called glucocorticosteroids or corticosteroids are
the mostly used anti-inflammatory immunosuppressive drugs
in many inflammatory immune and allergic diseases such are,
for example, ulcerative colitis, arthritis,
multiple sclerosis, eczema, psoriasis, allergy, and asthma.
Their activity is due to
complex molecular mechanisms responsible of therapeutic and adverse effects.
The benefit risk-ratio between therapeutic,
and the adverse effects is most important,
and these are the limiting factors of glucocorticoids therapeutic approach.
Now, we have to define what glucocorticoids drugs are.
But before the definition of glucocorticoids drugs,
we have to consider that there are endogenous glucocorticoids in our body.
Endogenous glucocorticoids are part of our physiological system where
endogenous hormones are produced physiologically under a strict regulation mechanism.
Endogenous glucocorticoids are mainly
produced in the zona fasciculata of the adrenal cortex,
and also at low concentration in some specific organs, including thymus,
intestine and glands, and their production is increased in response to stress.
Endogenous glucocorticoids production, in response to
many stimuli, is an important stress response system.
Acute increase of glucocorticoids levels
helps the body maintain homeostatic equilibrium,
including the metabolic, immune, and cardiovascular functions.
Their production in a circadian manner being higher in the morning is regulated by a
control feedback mechanism at the hypothalamic-pituitary adrenal axis, HPA level.
After production and release,
the blood level of free hormone available to enter cells are
further regulated by binding to corticosteroid binding protein, CBP,
and by tissue specific enzymatic activity.
Summarized as, CBP transports
the glucocorticoids in the body and releases it in different organs and tissues.
Moreover, specific enzyme activities contribute to
them to determine the actual glucocorticoids levels.
In fact, most glucocorticoids
specific effects, at the tissue and cell level, are fully regulated
by the 11-Beta hydroxysteroid dehydrogenase enzymes activity in the tissues.
Cortisol, the major endogenous glucocorticoid, diffuses from
the blood into the cells and interacts with glucocorticoid receptors, GRs,
thus exerting between others its anti-inflammatory effects.
Cortisol, in fact, can also be used as an anti-inflammatory drug.