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Immunophysiology: The Interaction of Hormones, Lymphohemopoietic Cytokines, and the Neuroimmune Axis

Sean Arkins, Rodney W. Johnson, Christian Minshall, Robert Dantzer, Keith W. Kelley

10.1002/cphy.cp070421

Source: Supplement 23: Handbook of Physiology, The Endocrine System, Coping with the Environment: Neural and Endocrine Mechanisms

Originally published: 2001

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Proinflammatory Cytokines Regulate the Hypothalamic‐Pituitary Adrenal Axis
2 Inflammatory Cytokines Regulate Secretion of Pituitary Growth Hormone
3 Cytokines and Their Receptors in the Central Nervous System
4 Cells in the Central Nervous System Synthesize Proinflammatory Cytokines
5 Receptors for Interleukin‐1 in the Central Nervous System
6 Receptors for Tumor Necrosis Factor in the Central Nervous System
7 Receptors for Interleukin‐6 in the Central Nervous System
8 Cytokines in the Central Nervous System Regulate Intermediary Metabolism
9 Synergistic Properties of Proinflammatory Cytokines
10 Growth Hormone and Prolactin: Pituitary Hormones Whose Receptors are Members of the Hematopoietin Receptor Superfamily
11 Growth Hormone and Insulin‐Like Growth Factor‐I
12 Insulin‐Like Growth Factor‐I Receptor: A Transmembrane Tyrosine Kinase
13 Immunological Actions of Growth Hormone and Insulin‐Like Growth Factor‐I: The Big Picture
14 Growth Hormone and Insulin‐Like Growth Factor‐I: Hematopoietic Cytokines?
14.1 Erythropoiesis
14.2 Lymphopoiesis
14.3 Myelopoiesis
15 Growth Hormone and Insulin‐Like Growth Factor‐I Demonstrate Classical Properties of Pleiotropic Lymphohemopoietic Cytokines
15.1 Promoting Cell Survival
15.2 Increasing DNA Synthesis
15.3 Enhancing Effector Functions
16 Hematopoietic Actions of Insulin‐Like Growth Factor‐I: Endocrine or Paracrine?
17 Clinical use of Recombinant Growth Hormone
18 Conclusion
Figure 1. Figure 1.

Bacterial infection attenuates somatic growth by inducing release of proinflammatory cytokines from leukocytes. Cytokines, such as IL‐1, TNF‐α, and IL‐6 induce proteolysis and lipolysis and also modulate pituitary GH secretion 89,90,232. The reduction in circulating GH is paralleled by an immediate decline in hepatic IGF‐I secretion and an increase in the serum levels of some IGF binding proteins (IGFBPs). The result is a reduction in the level of IGF‐I at the tissue level. In addition, cytokines have direct effects on hepatic metabolsim (see Table 1), including direct inhibitory effects on IGF‐I secretion, induction of acute phase protein synthesis, and glycogenolysis.

Reproduced from 141
Figure 2. Figure 2.

Effects of vagotomy on the LPS‐induced decrease in locomotor activity (upper) and increase in IL‐1β mRNA in hypothalamus (lower). As shown in the upper graph, subdiaphragmatic vagotomy prevented LPS‐induced sickness as indicated by locomotor activity during a 4‐min test. The lower graph shows that vagotomy prevented the LPS‐induced expression of IL‐1β in murine hypothalamus. Collectively, these data suggest a neural mechanism of communication between the peripheral immune system and CNS.

Adapted from 43,175
Figure 3. Figure 3.

Intracellular substrates and signaling pathways in IGF‐I signal transduction in myeloid cells occurs via the transmembrane IGF‐I receptor (IGF‐IR). Insulin‐like growth factor‐I regulates the activation of phosphatidylinositol 3′‐kinase (PI3‐K) in promyeloid cells by inducing the tyrosine phosphorylation of IRS‐1 and IRS‐2. The β subunit of the IGF‐IR directly phosphorylates IRS‐1 and −2 and subsequently activates PI3‐K. There are a number of well‐known downstream targets of PI3‐K, such as GLUT 4 glucose transporters, the 70 Kda ribosomal S6 kinase, some isotypes of protein kinase C, and the protein kinase B (Akt). The question marks signify that the complete pathways between 3′phosphorylated derivatives of PI and the regulation of biologically important genes is not yet fully understood. Insulin‐like growth factor‐I has also been shown to activate the ERK/MAPK pathway by interacting with Shc and the subsequent intermediate proteins, Grb‐2 and Sos. Activation of these pathways by IGF‐I may explain this growth factor's ability to promote survival, proliferation, and differentiation of hematopoietic cells.


Figure 1.

Bacterial infection attenuates somatic growth by inducing release of proinflammatory cytokines from leukocytes. Cytokines, such as IL‐1, TNF‐α, and IL‐6 induce proteolysis and lipolysis and also modulate pituitary GH secretion 89,90,232. The reduction in circulating GH is paralleled by an immediate decline in hepatic IGF‐I secretion and an increase in the serum levels of some IGF binding proteins (IGFBPs). The result is a reduction in the level of IGF‐I at the tissue level. In addition, cytokines have direct effects on hepatic metabolsim (see Table 1), including direct inhibitory effects on IGF‐I secretion, induction of acute phase protein synthesis, and glycogenolysis.

Reproduced from 141


Figure 2.

Effects of vagotomy on the LPS‐induced decrease in locomotor activity (upper) and increase in IL‐1β mRNA in hypothalamus (lower). As shown in the upper graph, subdiaphragmatic vagotomy prevented LPS‐induced sickness as indicated by locomotor activity during a 4‐min test. The lower graph shows that vagotomy prevented the LPS‐induced expression of IL‐1β in murine hypothalamus. Collectively, these data suggest a neural mechanism of communication between the peripheral immune system and CNS.

Adapted from 43,175


Figure 3.

Intracellular substrates and signaling pathways in IGF‐I signal transduction in myeloid cells occurs via the transmembrane IGF‐I receptor (IGF‐IR). Insulin‐like growth factor‐I regulates the activation of phosphatidylinositol 3′‐kinase (PI3‐K) in promyeloid cells by inducing the tyrosine phosphorylation of IRS‐1 and IRS‐2. The β subunit of the IGF‐IR directly phosphorylates IRS‐1 and −2 and subsequently activates PI3‐K. There are a number of well‐known downstream targets of PI3‐K, such as GLUT 4 glucose transporters, the 70 Kda ribosomal S6 kinase, some isotypes of protein kinase C, and the protein kinase B (Akt). The question marks signify that the complete pathways between 3′phosphorylated derivatives of PI and the regulation of biologically important genes is not yet fully understood. Insulin‐like growth factor‐I has also been shown to activate the ERK/MAPK pathway by interacting with Shc and the subsequent intermediate proteins, Grb‐2 and Sos. Activation of these pathways by IGF‐I may explain this growth factor's ability to promote survival, proliferation, and differentiation of hematopoietic cells.

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Article Title: Immunophysiology: The Interaction of Hormones, Lymphohemopoietic Cytokines, and the Neuroimmune Axis
 

How to Cite

Sean Arkins, Rodney W. Johnson, Christian Minshall, Robert Dantzer, Keith W. Kelley. Immunophysiology: The Interaction of Hormones, Lymphohemopoietic Cytokines, and the Neuroimmune Axis. Compr Physiol 2011, Supplement 23: Handbook of Physiology, The Endocrine System, Coping with the Environment: Neural and Endocrine Mechanisms: 469-495. First published in print 2001. doi: 10.1002/cphy.cp070421