The antiinflammatory properties of
glucocorticoids result basically from their inhibitory effect on synthesis of proinflammatory
proteins, in particular many
cytokines.
Corticoids reduce the production of
prostanoids by inhibiting the expression of COX-2, but are much less effective on the production of
leukotrienes.
Corticoids inhibit the degranulation of human basophils (histamine release) but have no effect on mast cells. 4. ACTIVATION OF A
CYTOPLASMIC RECEPTOR: The antiinflammatory effect of
glucocorticoids is mediated by binding to a
cytoplasmic receptor which, when activated, migrates to the nucleus. The activated receptor can interact with
transcription factors (NF-kappa B, AP-1) inhibiting the synthesis of proinflammatory
proteins (cytokines, COX-2...). This "transrepressive" activity explains most of the antiinflammatory effects of
glucocorticoids. 5. ACTION OF THE ACTIVATED RECEPTOR: The activated receptor can bind to specific sites present on the regulator region of target genes, inducing their transcription (or transactivation). This induction effect on
protein synthesis concerns the renin-angiotensin system, neoglucogenesis, and bone metabolism. Increased production of these
proteins explain the metabolic and endocrine effects of
glucocorticoids which, when exaggerated, particularly with general administration, can lead to undesirable effects. At the present time, our knowledge suggests it would be best to have molecules with a predominant transrepressive activity (antiinflammatory activity) since the
transactivator effects appeared to be associated with the undesirable metabolic effects of
glucocorticoids. 6. OTHER
PHARMACEUTICAL PROPERTIES:
Glucocorticoids also have properties that do not require gene expression. These "non-genomic" effects could occur at high dosage "pulse"
therapy. We will have to wait for more pertinent clinical information on these effects to use the power of these non-genomic effects to guide our choice of the appropriate
glucocorticoid in given clinical situations. 7. LOCAL TREATMENT FOR
ALLERGIC RHINITIS: Given locally
glucocorticoids reduce the concentration of many inflammatory mediators and the number of inflammatory cells in secretions and nasal biopsies. The efficacy of
glucocorticoids is perfectly established in this indication as well as in nasal polyposis. 8. LOCAL TOLERANCE: During the first days of treatment, local application of
corticoids on the inflammatory mucosal surface can cause irritation and/or
sneezing. These manifestations generally subside in a few days and are more frequent with solutions containing glycol. The dry nose sensation, sometimes associated with minimal
epistaxis, is classically reported, though at a low frequency. A few rare cases of ulceration of perforation of the septum have been report and it would be difficult to exclude a mechanical cause related to administration route. It is clear that the risk of mucosal
atrophy has been eliminated with the use of nasal
corticosteroids. 9. EVALUATION OF THE SYSTEMIC EFFECT OF NASAL
CORTICOSTEROIDS: Most of the studies have examined the hypothalamo-pituitary-adrenal axis. These studies have rarely demonstrated, an then in isolated cases, any significant modification at recommended doses. Likewise for other markers of passage into the systemic circulation such as osteocalcine or the number of circulating eosinophils. There is also very little risk of growth impairment in children or
cataracts in adults. 10. SHORT-COURSE GENERAL
CORTICOSTEROID THERAPY: Short periods are sometimes recommended for
rhinitis,
sinusitis, polyposis or
laryngitis. Use of a short duration treatment (about one week) at doses in the 1 mg/kg/d range, induce a transient inhibition of the corticoadrenal axis in about half the patients; this inhibition disappears in most all cases in two weeks. The clinical risk associated with this alteration in patients under stress (
infection,
trauma...) remains hypothetical. In any case, it would be advisable to avoid repeating short-course general
corticosteroid therapy at close intervals.