The AAPS Journal

, Volume 7, Issue 4, pp E865–E870

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

  • Martin W. Adler
  • Ellen B. Geller
  • Xiaohong Chen
  • Thomas J. Rogers
Article

DOI: 10.1208/aapsj070484

Cite this article as:
Adler, M.W., Geller, E.B., Chen, X. et al. AAPS J (2005) 7: E865. doi:10.1208/aapsj070484

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.

Keywords

opioidscannabinoidschemokinesbraindesensitizationneurotransmitters

Copyright information

© American Association of Pharmaceutical Scientists 2005

Authors and Affiliations

  • Martin W. Adler
    • 3
    • 2
  • Ellen B. Geller
    • 3
  • Xiaohong Chen
    • 3
  • Thomas J. Rogers
    • 3
    • 1
    • 2
  1. 1.Fels Institute for Cancer Research and Molecular BiologyTemple University School of MedicinePhiladelphia
  2. 2.Department of PharmacologyTemple University School of MedicinePhiladelphia
  3. 3.Center for Substance Abuse ResearchTemple University School of MedicinePhiladelphia