Regulation of IGF-I function by proinflammatory cytokines: at the interface of immunology and endocrinology.
During the past decade, the immune and endocrine systems have been discovered to interact in controlling physiologic processes as diverse as cell growth and differentiation, metabolism, and even human and animal behavior. The interaction between these two major physiological systems is a bi-directional process. While it has been well documented that hormones, including prolactin (PRL), growth hormone (GH), insulin-like growth factor-I (IGF-I), and thyroid-stimulating hormone (TSH), regulate a variety of immune events, a great deal of data have accumulated supporting the notion that cytokines from the innate immune system also affect the neuroendocrine system. Communication between these two systems coordinates processes that are necessary to maintain homeostasis. Proinflammatory cytokines often act as negative regulatory signals that temper the action of hormones and growth factors. This system of 'checks and balances' is an active, ongoing process, even in healthy individuals. Dysregulation of this process has been implicated as a potential pathogenic factor in the development of co-morbid conditions associated with several chronic inflammatory diseases, including type 2 diabetes, cardiovascular disease, cerebrovascular disease, inflammatory bowel disease, rheumatoid arthritis, major depression, and even normal aging. Over the past decade, research in our laboratory has focused on the ability of the major proinflammatory cytokines, tumor necrosis factor (TNF)alpha and interleukin (IL)-1beta, to induce a state of IGF resistance. This review will highlight these and other new findings by explaining how proinflammatory cytokines induce resistance to the major growth factor, insulin-like growth factor-I (IGF-I). We also highlight that IGF-I can induce resistance or reduce sensitivity to brain TNFalpha and discuss how TNFalpha, IL-1beta, and IGF-I interact to regulate several aspects of behavior and cognition.
O'Connor
Jason C
JC
Integrative Immunology and Behavior Program, Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
McCusker
Robert H
RH
Strle
Klemen
K
Johnson
Rodney W
RW
Dantzer
Robert
R
Kelley
Keith W
KW
D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I