Panoramic View of Glucocorticoids’ Actions on the Immune Response: A Good Model to Understand Immunosuppression for New Treatment Strategies

D. Franchimont

Gastroenterology Department, Erasme University Hospital, Brussels, Belgium.

Glucocorticoids have been used for over 50 years in the treatment of inflammatory and autoimmune diseases and in preventing graft rejection. Integrating molecular, cellular and pharmacological knowledge allows a better understanding of glucocorticoid - mediated immunosuppression. Gene profiling revealed that glucocorticoids exert both negative and positive effects at the same time with a dynamic and bi-directional spectrum of activities on various limbs and components of the immune response. Glucocorticoids modulate genes involved in the priming of the innate immune response, while their actions on the adaptive immune response are to suppress cellular (Th1-directed) immunity and promote humoral (Th2-directed) immunity. Indeed, this explains the beneficial and adverse effects of glucocorticoids on the immune response. They restrain inflammation and prevent tissue destruction, but can increase susceptibility to opportunistic infections, and trigger or worsen inflammatory diseases. Interestingly, glucocorticoids can also induce tolerance to specific antigens by influencing dendritic cell phenotype and promoting the development of regulatory high-IL-10 producing T cells. The ex-vivo therapeutic use of glucocorticoids could therefore represent an adjuvant treatment to cell therapy in autoimmune diseases, avoiding long-term deleterious adverse effects of glucocorticoids. Thus, a panoramic view of glucocorticoids' actions on the immune system provides an interesting model for characterizing immunomodulation pathways. This glucocorticoid-mediated immune profiling appears useful in order to find new gene targets for novel immunosuppressants and to facilitate the identification of new molecular pharmacogenomic markers that predict and monitor response to treatment.