Fifty years of experience with cortisone therapy in the study and treatment of rheumatoid arthritis.
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.
Department of Internal Medicine, Division of Rheumatology and Clinical Immunology, Rostock Clinic South, Rostock, Germany. kfim@kliniksued-rostock.de
Gunther
G
Neeck
D000893:Anti-Inflammatory Agents / Q000266:history* / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000266:history* / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000266:history*; D003348:Cortisone / Q000266:history / Q000502:physiology; D005938:Glucocorticoids / Q000266:history* / Q000494:pharmacology / Q000627:therapeutic use; D049673:History, 20th Century; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D003348:Cortisone