Multiple neuropeptides in nerves supplying mammalian lymph nodes: messenger candidates for sensory and autonomic neuroimmunomodulation?

Neurosci Lett. 1988 Jul 19;90(1-2):39-44. doi: 10.1016/0304-3940(88)90783-5.


By the use of light microscopic (LM) immunohistochemistry, the presence of peptides and of dopamine beta-hydroxylase (DBH) in nerves supplying mammalian (guinea pig, rat, cat, pig, mouse, human) lymph nodes were examined. In all species, lymph nodes of various somatic and visceral regions were found to contain nerve fibers which stained for neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), substance P (SP), calcitonin gene-related peptide (CGRP) or DBH. SP- and CGRP-immunoreactive (ir) fibers completely overlapped and exhibited the widest distribution. They were present in perivascular, paravascular and many non-vascular fibers travelling in close contact with lymphoid cells. In contrast, NPY-ir fibers coincided with those staining for DBH, prevailed in perivascular plexus and only rarely branched off into lymphoid parenchyma. Alternate staining of adjacent sections revealed that SP/CGRP-ir fibers were different from NPY/DBH-ir fibers. The distribution of VIP-ir fibers was identical to that of PHI-ir fibers and partially overlapped with that of ir-NPY/DBH or ir-SP/CGRP fibers. We conclude that the NPY innervation of lymph nodes is sympathetic noradrenergic while nerves coding for co-existing SP and CGRP are most likely of sensory origin. The nerves containing co-existing VIP and PHI may be of heterogenous origin (sensory, cholinergic sympathetic, and/or parasympathetic). We suggest that these distinct sensory and autonomic peptidergic pathways linking the nervous system with the lymph nodes may play a differential role in bidirectional neuroimmunomodulation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Fibers / analysis*
  • Animals
  • Blood Vessels / innervation
  • Cats
  • Guinea Pigs
  • Humans
  • Lymph Nodes / blood supply
  • Lymph Nodes / innervation*
  • Mice
  • Neurons, Afferent / analysis*
  • Neuropeptide Y / analysis
  • Neuropeptides / analysis*
  • Peptide PHI / analysis
  • Rats
  • Species Specificity
  • Substance P / analysis
  • Swine
  • Vasoactive Intestinal Peptide / analysis


  • Neuropeptide Y
  • Neuropeptides
  • Peptide PHI
  • Substance P
  • Vasoactive Intestinal Peptide