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Review ArticleReview Article

Insulin-Like Growth Factor-I Regulation of Immune Function: A Potential Therapeutic Target in Autoimmune Diseases?

Terry J. Smith
Pharmacological Reviews June 2010, 62 (2) 199-236; DOI: https://doi.org/10.1124/pr.109.002469
Terry J. Smith
Division of Molecular Medicine, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California; the David Geffen School of Medicine at UCLA, Los Angeles, California; and Departments of Ophthalmology and Visual Sciences and Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan
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Abstract

This topically limited review explores the relationship between the immune system and insulin-like growth factors (IGF-I and IGF-II) and the proteins through which they act, including IGF-I receptor (IGF-IR) and the IGF-I binding proteins. The IGF/IGF-IR pathway plays important and diverse roles in tissue development and function. It regulates cell cycle progression, apoptosis, and the translation of proteins. Many of the consequences ascribed to IGF-IR activation result from its association with several accessory proteins that are either identical or closely related to those involved in insulin receptor signaling. Relatively recent awareness that IGF-I and IGF-IR regulate immune function has cast this pathway in an unexpected light; it may represent an important switch governing the quality and amplitude of immune responses. IGF-I/IGF-IR signaling may also participate in the pathogenesis of autoimmune diseases, although its relationship with these processes seems complex and relatively unexplored. On the one hand, IGF-I seems to protect experimental animals from developing insulin-deficient diabetes mellitus. In contrast, activating antibodies directed at IGF-IR have been detected in patients with Graves' disease, where the receptor is overexpressed by multiple cell types. The frequency of IGF-IR+ B and T cells is substantially increased in patients with that disease. Potential involvement of IGF-I and IGF-IR in the pathogenesis of autoimmune diseases suggests that this pathway might constitute an attractive therapeutic target. IGF-IR has been targeted in efforts directed toward drug development for cancer, employing both small-molecule and monoclonal antibody approaches. These have been generally well-tolerated. Recognizing the broader role of IGF-IR in regulating both normal and pathological immune responses may offer important opportunities for therapeutic intervention in several allied diseases that have proven particularly difficult to treat.

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  • This article is available online at http://pharmrev.aspetjournals.org.

    doi:10.1124/pr.109.002469.

  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 62 (2)
Pharmacological Reviews
Vol. 62, Issue 2
1 Jun 2010
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Review ArticleReview Article

Insulin-Like Growth Factor-I Regulation of Immune Function: A Potential Therapeutic Target in Autoimmune Diseases?

Terry J. Smith
Pharmacological Reviews June 1, 2010, 62 (2) 199-236; DOI: https://doi.org/10.1124/pr.109.002469

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Review ArticleReview Article

Insulin-Like Growth Factor-I Regulation of Immune Function: A Potential Therapeutic Target in Autoimmune Diseases?

Terry J. Smith
Pharmacological Reviews June 1, 2010, 62 (2) 199-236; DOI: https://doi.org/10.1124/pr.109.002469
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  • Article
    • Abstract
    • I. Introduction
    • II. Structure and Biology of Insulin-Like Growth Factor-I, Insulin-Like Growth Factor Receptor, and Insulin-Like Growth Factor-I Binding Proteins
    • III. Emerging Insights into Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-I Receptor: Roles in Immune Integration
    • IV. Impact of Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-I Receptor on Immune Cell Lineages
    • V. Implications of Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-I Receptor in Immune Modulation
    • VI. Insulin-Like Growth Factor-I, Insulin-Like Growth Factor-I Receptor, and Autoimmunity
    • VII. Therapeutic Horizons for Autoimmunity: Focusing on Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-I Receptor
    • VIII. Translational Strategies for Modulation of Insulin-Like Growth Factor-I or Insulin-Like Growth Factor-I Receptor
    • IX. Conclusions
    • Acknowledgments.
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    • References
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