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Viewing chemokines as a third major system of communication in the brain

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Abstract

There is irrefutable proof that opioids and other classes of centrally acting drugs have profound effects on the immune system. Evidence is mounting that products of the immune system, such as chemokines, can reciprocally alter the actions of these drugs and the endogenous ligands for their receptors. Chemokines are a family of small (8 to 12 kDa) proteins involved in cellular migration and intercellular communication. With a few exceptions, they act on more than one receptor. Although the chemokines and their G protein-coupled receptors are located in both glia and neurons throughout the brain, they are not uniformly distributed. They are found in such brain areas as the hypothalamus, nucleus accumbens, limbic system, hippocampus, thalamus, cortex, and cerebellum. Among the chemokines differentially localized in brain neurons and glia are CCL2/MCP-1, CXCL12/SDF-1α, CX3CL1/fractalkine, CXCL10/IP 10, CCL3/MIP-1α, and CCL5/RANTES. Functional roles for the chemokine system, composed of the chemokine ligands and their receptors, have been suggested in brain development and heterologous desensitization. The system can alter the actions of neuronally active pharmacological agents such as opioids and cannabinoids and interact with neurotransmitter systems. In this review, we propose that the endogenous chemokine system in the brain acts in concert with the neurotransmitter and neuropeptide systems to govern brain function. It can thus be thought of as the third major system in the brain.

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Authors and Affiliations

  1. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 19140, Philadelphia, PA

    Thomas J. Rogers

  2. Department of Pharmacology, Temple University School of Medicine, 19140, Philadelphia, PA

    Martin W. Adler & Thomas J. Rogers

  3. Center for Substance Abuse Research, Temple University School of Medicine, 3400 North Broad Street, 19140, Philadelphia, PA

    Martin W. Adler, Ellen B. Geller, Xiaohong Chen & Thomas J. Rogers

Authors
  1. Martin W. Adler
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  2. Ellen B. Geller
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  3. Xiaohong Chen
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  4. Thomas J. Rogers
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Corresponding author

Correspondence to Martin W. Adler.

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Published: January 6, 2006

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Adler, M.W., Geller, E.B., Chen, X. et al. Viewing chemokines as a third major system of communication in the brain. AAPS J 7, 84 (2005). https://doi.org/10.1208/aapsj070484

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  • DOI: https://doi.org/10.1208/aapsj070484

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