The effects of endogenous interleukin-1 bioactivity on locus coeruleus neurons in response to bacterial and viral substances.
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.
Borsody
Mark K
MK
Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Emory West Campus, 1256 Briarcliff Road, N.E., Atlanta, GA 30306, USA. mborsody@hotmail.com
Weiss
Jay M
JM
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D005260:Female; D007274:Injections, Intraperitoneal / Q000379:methods; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000166:cytology* / Q000382:microbiology / Q000821:virology; D008845:Microinjections / Q000379:methods; D009474:Neurons / Q000187:drug effects* / Q000382:microbiology / Q000502:physiology / Q000821:virology; D010457:Peptidoglycan / Q000494:pharmacology*; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000008:administration & dosage; D013997:Time Factors
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D012795:Sialoglycoproteins