Meir Djaldetti, Chiya Moshe Leibovitch, Hanna Bessler
Background: The introduction of glucocorticoids (GCS) in medical practice made a revolution in the treatment of auto-immune diseases and inflammatory disorders. GCS repress inflammatory processes by their ability to modulate cytokine production by macrophages that are the main cohort of cells invading inflammatory sites. This effect is concentration- and activity-duration dependent and accordingly GCS are designated as brands with short, intermediate and long activity. The aim of the study was to examine the effect of hydrocortisone (HC), prednisone (Pred) and dexamethasone (Dexa) as representatives of the three groups respectively, on the capability of human peripheral blood mononuclear cells (PBMC) to produce cytokines and to detect their influence on the immune dialogue between PBMC and HT-29 cells from a human colon carcinoma line. Methods: Not-stimulated PBMC or cells stimulated with either LPS or PMA/ionomycin were incubated without or with one of the tree GCS at two concentrations calculated according to their relative potency. The production of TNFα, IL-1β, IL-6, IFNγ, IL-2, and IL-10 was assessed. In another set of experiments PBMC were co-cultured with HT-29 human colon carcinoma cells in absence or presence of GCS and the secretion of the abovementioned cytokines was evaluated. Results: Not-stimulated PBMC did react to Pred (intermediate acting) and Dexa (long-acting) by inhibited TNFα secretion at the lower concentrations only. Stimulated PBMC incubated separately with the three GCS showed repressed production of all cytokines except for IL-6 that was not affected by HC and IL-10 whose production was influenced by Pred only. PBMC co-incubated with HT-29 cells showed inhibited secretion of TNFα and IL-1β under the effect of all three GCS, whereas that of IL-6 and IFNγ was constrained by Pred and HC. Conclusions: The findings indicate that GCS of the three groups suppress the production of inflammatory cytokines rather comparably and only prednisone exerts this effect on the generation of the pro-inflammatory IL-6 and the anti-inflammatory IL-10. These observations may help reaching a suitable decision as for the type of GCS to be used in certain medical conditions.
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