The effects of endogenous interleukin-1 bioactivity on locus coeruleus neurons in response to bacterial and viral substances

• Published in: Brain research Vol. 1007; no. 1; pp. 39 - 56
• Main Authors: Borsody, Mark K., Weiss, Jay M.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 08.05.2004; Amsterdam Elsevier; New York, NY
• Subjects: Action Potentials - drug effects; Analysis of Variance; Animals; Biochemistry and metabolism; Biological and medical sciences; Central nervous system; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Interactions; Female; Fundamental and applied biological sciences. Psychology; IL-1RA; Injections, Intraperitoneal - methods; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-1 - metabolism; Interleukin-1 - physiology; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Locus coeruleus; Locus Coeruleus - cytology; Locus Coeruleus - microbiology; Locus Coeruleus - virology; Microinjections - methods; Neurons - drug effects; Neurons - microbiology; Neurons - physiology; Neurons - virology; Peptidoglycan; Peptidoglycan - pharmacology; Physical Stimulation - methods; Poly(I)/(C); Rats; Rats, Sprague-Dawley; Sialoglycoproteins - administration & dosage; Time Factors; Vertebrates: nervous system and sense organs; Peptidoglycan; Interleukin-1; Neural–immune interactions; IL-1RA; Poly(I)/(C); Endocrine and autonomic regulation; Lipopolysaccharide; Locus coeruleus; Rat; Cytokine; Rodentia; Central nervous system; Biological activity; Encephalon; Virus; Vertebrata; Mammalia; Neuron; Interleukin 1; Bacteria
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2004.02.011

In a previous study, we found that microinjection of the cytokine interleukin-1 (IL-1) into the locus coeruleus (LC) increased the electrophysiological activity of LC neurons. To determine if endogenous IL-1 similarly affects the LC, brain IL-1 was induced with lipopolysaccharide (LPS), a substance derived from Gram-negative bacteria. LPS microinjected directly into the LC increased the activity of LC neurons in anesthetized rats, and this effect was blocked by microinfusion of the IL-1 receptor antagonist (IL-1RA) protein into the LC indicating the involvement of IL-1 receptors. Similarly, intraperitoneal (i.p.) LPS injection increased the activity of LC neurons in a dose- and time-related manner that was sensitive to IL-1RA. The change in the activity of LC neurons caused by a single i.p. injection of LPS was surprisingly long-lasting, and evolved over a period of at least 3 weeks. Other microbial substances—namely, peptidoglycan from Gram-positive bacteria and poly-inosine/poly-cytosine (poly(I)/(C)), which resembles RNA viruses—were used to determine the generality of the findings with LPS. Both i.p. peptidoglycan and poly(I)/(C) increased LC activity but with lesser efficacy than LPS. IL-1RA reversed the increase in the activity of LC neurons caused by i.p. peptidoglycan treatment; however, that caused by i.p. Poly(I)/(C) was not diminished by IL-1RA. Thus, the increased activity of LC neurons caused by LPS and peptidoglycan requires IL-1 receptor binding, suggesting the involvement of endogenously-produced IL-1. In contrast, poly(I)/(C) increased the activity of LC neurons but this did not critically involve IL-1 receptors in the LC.