Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies.

From the Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bldg. 10, Rm. 10N262, Bethesda, MD 20892, where reprint requests should be addressed to Dr. Chrousos. C ELSUS described four of the five cardinal signs of inflammation 2000 years ago, and Eustachio discovered the adrenal glands almost 500 years ago, but not until 1936 did Selye note that in rats exposed to stressors, the adrenal glands were enlarged, and the thymus and lymph nodes shrunken. 1-3 Cortisone, the active principle of the adrenal glands, was isolated by Kendall and Reichstein in the late 1940s and shown to suppress immune organs. These scientists, along with Hench, received the Nobel Prize in Physiology and Medicine, after Hench and colleagues showed that cortisone could ameliorate rheumatoid arthritis. 4,5 In recent years, our understanding of the interactions between the hypothalamic–pituitary–adrenal (HPA) axis and immune-mediated inflammatory reactions has expanded enormously. This review outlines the influences that the HPA axis and immune-mediated inflammatory reactions exert on each other and discusses the implications of these interactions for human disease.