Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Nov 1;89(21):10440–10443. doi: 10.1073/pnas.89.21.10440

Cultured sympathetic neurons synthesize and release the cytokine interleukin 1 beta.

M Freidin 1, M V Bennett 1, J A Kessler 1
PMCID: PMC50354  PMID: 1279679

Abstract

Autonomic neurons help to regulate immune responses, and there are reciprocal interactions between the nervous and immune systems. This study seeks to define some of the molecular mechanisms that may underlie such interactions. Immunoblot analysis indicated that cultured sympathetic neurons synthesize and release the cytokine interleukin 1 beta (IL-1 beta). In addition, RNA blot analysis of cultured sympathetic neurons demonstrated that the neurons contain mRNA encoding IL-1 beta. It was previously shown that explant cultures of sympathetic ganglia and dissociated cocultures of neurons with ganglionic nonneuronal cells synthesize substance P, whereas in situ levels of substance P and its mRNA are low. An antagonist at the interleukin 1 receptor markedly depressed this increase in substance P in cultures, suggesting that endogenous IL-1 beta mediates the synthetic response, at least in part. Because pure neuronal cultures do not contain substance P and neurons synthesize and release IL-1 beta, the actions of the cytokine require the presence of ganglion nonneuronal cells. These observations suggest a role for autonomic neurons in influencing immune responses by synthesizing and secreting at least two known immunoregulators, the cytokine IL-1 beta and the neuropeptide substance P.

Full text

PDF
10440

Images in this article

10441Image
on p.10441
10441Image
on p.10441
10442Image
on p.10442

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bandtlow C. E., Meyer M., Lindholm D., Spranger M., Heumann R., Thoenen H. Regional and cellular codistribution of interleukin 1 beta and nerve growth factor mRNA in the adult rat brain: possible relationship to the regulation of nerve growth factor synthesis. J Cell Biol. 1990 Oct;111(4):1701–1711. doi: 10.1083/jcb.111.4.1701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  3. Dinarello C. A. Dissociation of transcription from translation of human IL-1 beta: induction of steady state mRNA by adherence or recombinant C5a in the absence of translation. Proc Soc Exp Biol Med. 1992 Jun;200(2):228–232. doi: 10.3181/00379727-200-43425. [DOI] [PubMed] [Google Scholar]
  4. Dinarello C. A. Interleukin-1. Ann N Y Acad Sci. 1988;546:122–132. doi: 10.1111/j.1749-6632.1988.tb21627.x. [DOI] [PubMed] [Google Scholar]
  5. Dinarello C. A., Savage N. Interleukin-1 and its receptor. Crit Rev Immunol. 1989;9(1):1–20. [PubMed] [Google Scholar]
  6. Eisenberg S. P., Evans R. J., Arend W. P., Verderber E., Brewer M. T., Hannum C. H., Thompson R. C. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature. 1990 Jan 25;343(6256):341–346. doi: 10.1038/343341a0. [DOI] [PubMed] [Google Scholar]
  7. Freidin M., Kessler J. A. Cytokine regulation of substance P expression in sympathetic neurons. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3200–3203. doi: 10.1073/pnas.88.8.3200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hannum C. H., Wilcox C. J., Arend W. P., Joslin F. G., Dripps D. J., Heimdal P. L., Armes L. G., Sommer A., Eisenberg S. P., Thompson R. C. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. doi: 10.1038/343336a0. [DOI] [PubMed] [Google Scholar]
  9. Jonakait G. M., Schotland S., Hart R. P. Interleukin-1 specifically increases substance P in injured sympathetic ganglia. Ann N Y Acad Sci. 1990;594:222–230. doi: 10.1111/j.1749-6632.1990.tb40482.x. [DOI] [PubMed] [Google Scholar]
  10. Kessler J. A., Adler J. E., Black I. B. Substance P and somatostatin regulate sympathetic noradrenergic function. Science. 1983 Sep 9;221(4615):1059–1061. doi: 10.1126/science.6192502. [DOI] [PubMed] [Google Scholar]
  11. Kessler J. A. Differential regulation of peptide and catecholamine characters in cultured sympathetic neurons. Neuroscience. 1985 Jul;15(3):827–839. doi: 10.1016/0306-4522(85)90081-8. [DOI] [PubMed] [Google Scholar]
  12. Kessler J. A., Freidin M. Regulation of substance P expression in sympathetic neurons. Ann N Y Acad Sci. 1991;632:10–18. doi: 10.1111/j.1749-6632.1991.tb33089.x. [DOI] [PubMed] [Google Scholar]
  13. Kimball E. S., Fisher M. C. Potentiation of IL-1-induced BALB/3T3 fibroblast proliferation by neuropeptides. J Immunol. 1988 Dec 15;141(12):4203–4208. [PubMed] [Google Scholar]
  14. Kimball E. S. Substance P, cytokines, and arthritis. Ann N Y Acad Sci. 1990;594:293–308. doi: 10.1111/j.1749-6632.1990.tb40489.x. [DOI] [PubMed] [Google Scholar]
  15. Lindholm D., Heumann R., Meyer M., Thoenen H. Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve. Nature. 1987 Dec 17;330(6149):658–659. doi: 10.1038/330658a0. [DOI] [PubMed] [Google Scholar]
  16. Nawa H., Nakanishi S., Patterson P. H. Recombinant cholinergic differentiation factor (leukemia inhibitory factor) regulates sympathetic neuron phenotype by alterations in the size and amounts of neuropeptide mRNAs. J Neurochem. 1991 Jun;56(6):2147–2150. doi: 10.1111/j.1471-4159.1991.tb03479.x. [DOI] [PubMed] [Google Scholar]
  17. Takao T., Tracey D. E., Mitchell W. M., De Souza E. B. Interleukin-1 receptors in mouse brain: characterization and neuronal localization. Endocrinology. 1990 Dec;127(6):3070–3078. doi: 10.1210/endo-127-6-3070. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES