Regulation of IGF-I function by proinflammatory cytokines: At the interface of immunology and endocrinology

Abstract

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.

Growth factor and cytokine interactions in myogenesis. Part I. The effect of TNF-α and IFN-γ on IGF-I-dependent differentiation in mouse C2C12 myogenic cells

“…TNF-α has already been shown to inhibit IGF-I-stimulated hypertrophy of C2C12 cells (assessed by MHC levels) and expression of two critical myogenic regulatory factors -MyoD and myogenin in C2C12 myoblasts (O'Connor et al 2008). The lack of evident changes in cellular content of myogenin under cytokine treatment presented in our study (Fig.…”

GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

“…GH and IL6 receptors belong to the class I cytokine receptors, which show structural similarities and share intracellular regulatory pathways, thereby implying the possibility of various intracellular interactions between IL6, GH, and their receptors (45,46). For IGF1, similar intracellular cross talks have been suggested primarily linking IGF1 and TNFa activity (4,8,42).…”

“…An increasing amount of data has supported a connection between the innate immune system and the activity of the GH/insulin-like growth factor 1 (IGF1) axis (1,2,3,4). The vast majority of clinical and experimental studies have focused on stages with increased inflammation where it seems that chronic inflammation suppresses the GH/IGF1 axis (2,5,6,7,8,9).…”

Imunologia do transtorno bipolar

“…Vários fatores provavelmente contribuem para a indefinição acerca do envolvimento de fatores imunes no TB, como o volume limitado de pesquisas realizadas, especialmente investigando pacientes bipolares nas três fases da doença, o que poderia demonstrar um perfil imunológico distinto em cada uma delas, e o pequeno número de pacientes incluídos nos estudos. Outro possível fator limitante seria a ausência de informação sobre as comorbidades clíni-cas e psiquiátricas dos pacientes que poderiam interferir em parâmetros imunes como, por exemplo, diabetes mellitus 45 , doenças coronarianas 46 , obesidade 47 , tabagismo 48 , esclerose múltipla 49 e transtorno obsessivo-compulsivo 12 . Dessa forma, os próximos estudos deverão ser mais criteriosos no recrutamento das populações com TB.…”