From hormones to immunity: the physiology of immunology.

Discoveries in the physiology of immunology have increased at an increasing rate during the past two decades. It is now recognized that the immune system is just another physiological system that regulates, and is regulated by, other physiological systems such as the brain. These advances make it clear that recent findings in genomic biology must be interpreted in the context of the environment in which animals and humans live. Lack of a strong genetic basis for significant human mental health disorders, such as major depression, points to the critical importance of interactions. Several examples of environmental x genetic x disease interactions are presented. Regulation of cells of the hematopoietic lineage by two genes that control over 80% of postnatal growth, growth hormone and IGF-I, are then highlighted. The reciprocal relationship of how proinflammatory cytokines from the immune system regulate the growth hormone/IGF-I axis is also summarized. Particular emphasis is placed upon TNFalpha-induced IGF-I resistance in neurons, muscle cells and epithelial cells. This cytokine regulation of hormone action may ultimately be more important for human and animal health than direct effects of growth hormone and IGF-I on hematopoietic cells. Wasting of AIDS patients is given as an important clinical example of how TNFalpha from an activated immune system reduces IGF-I sensitivity in multiple physiologic systems, including muscle, nervous and hematopoietic tissues.