In 1948 the U.S. rheumatologist Phillip S. Hench administered
cortisone for the first time to a patient with
rheumatoid arthritis (RA), thereby discovering the
therapeutic effects of
glucocorticoids. He published this observation together with Kendall, Slocumb, and Polly in 1949, and they received, along with Reichstein and Kendall, the Nobel Prize in Medicine or Physiology in 1950. However, as early as 1949, he rejected the idea that
steroids were of etiological significance for RA, and instead stressed their unique place as a tool for pathophysiological research. The discovery of the
glucocorticoid receptor and its genomic effects disclosed that there are no qualitative differences between the effects of endogenous
cortisol and exogenously applied synthetic
glucocorticoids, since all effects are transmitted via the same receptor. Later came the discovery that the hypothalamo-pituitary-adrenal axis is stimulated by
cytokines after activation of the immune system.
Glucocorticoids are not only the most effective antiphlogistic and immune-suppressive substances with instant effect, but they also show, with low-dosage long-term treatment, clear antiproliferative effects on the cartilage and bone destroying pannus in RA. Little is still known about the precise mechanisms of actions of
glucocorticoids in general, and specifically when rheumatic
autoimmune diseases are involved. The high effectiveness of these substances and their direct effects via the genomic
glucocorticoid receptor allows us to anticipate that uncovering their mechanisms of action will shed deeper insight into the pathomechanisms of these diseases. The use of
TNFalpha blockers in the treatment of
rheumatoid arthritis and
Crohn's disease, with their dramatic immediate effects, comparable with those of the
glucocorticoids but without the side effects of the latter, points us in that direction.