The nervous system and the immune system are connectedanatomically (1) and physiologically (2, 3). In this issue of the Proceedings, Pham-Dinh et al.(4) confirm that myelin/oligodendrocyte glycoprotein (MOG) is a member of the immunoglobulin gene superfamily (5) and demonstrate that the gene encoding MOG maps to the major histocompatibility complex (MHC). These observations extend our view of the interrelationships between the nervous system and the immune system.

The interactions between the nervous system and the immune system are ex-tensive. The basic mechanism underlying fever is a prime example of this interplay between immunity and the brain. Infec-tion causes macrophages to produce interleukin 1, which enters the hypothala-mus through a breach in the blood-brain barrier in the preoptic area. There it triggers arise in body temperature. Other factors, including infection, trauma, and stress, can act through the hypothalamic-pituitary axis to influence the immune system. Inflammation stimulates the re-lease of cytokines such as tumor necrosis factor, interleukin 1, and interleukin 6, which can trigger the release of corticotropin-releasing factor by the hypothalamus (6, 7). Corticotropin-releasing factor can stimulate the pituitary to produce adrenocorticotropin, ACTH, which circulates to the adrenal glands and stimulates the release of cortisol. Cortisol in turn may suppress immune responses and cause thymic involution. Corticotropin-releasing factor also has a paradoxi-cal effect on lymphocytes at the site of inflammation, where it heightens inflam-matory responses. In experimental ani-mals, failure to release normal levels of corticotropin-releasing factorin response to stress is correlated with susceptibility to experimentally induced autoimmunity (8). Recently Wilder, Chrousos, and col-leagues (39) have demonstrated that cor-ticotropin-releasing factor is present in the synovial fluid and tissues of patients with rheumatoid arthritis. Immune mediators such as yinter-feron have been known for some time to induce the expression ofimmune systemrelated molecules, such as MHC class I and class II molecules, on neurons, glial cells, and even muscle (9). The response to yinterferon allows glial cells, myo-