IL-1 beta depresses respiration and anoxic survival via a prostaglandin-dependent pathway in neonatal rats.
IL-1 beta has been proposed to be an important mediator linking infection, apnea, and sudden infant death syndrome. We hypothesized that IL-1 beta acts in this capacity by depressing brainstem respiratory neurons via a prostaglandin-dependent pathway. For studying the effects of IL-1 beta on respiration as well as the mechanism underlying its actions, 7-d-old rats received an initial injection (i.p.) of NaCl or a cyclooxygenase inhibitor (indomethacin, 10 mg/kg) followed by a second injection (i.p.) at 30 min of NaCl, recombinant rat IL-1 beta (10 microg/kg), or lipopolysaccharide (LPS; 100 microg/kg). Respiration during normoxia and in response to anoxia (100% N2) was examined at 60 min after the second injection using flow and barometric plethysmography. Animals given IL-1 beta breathed more slowly and died more often after anoxia. LPS also reduced the rats' ability to autoresuscitate and survive an anoxic challenge. Indomethacin prevented the depressive effects during normoxia and the adverse effects on survival. For investigating drug-induced changes in central respiratory activity, IL- 1 beta (1.0 or 1.25 ng/mL) and prostaglandin E2 (5 or 20 microg/L) was applied to the brainstem-spinal cord preparation of 0- to 4-d-old rats. Whereas IL-1 beta exerted no effect on respiration measured at the C4 ventral root during a 60-min period, prostaglandin E2 reversibly inhibited respiratory activity. These findings suggest that IL-1 beta does not inhibit respiratory neurons directly but may depress breathing and hypoxic defense via a prostaglandin-mediated mechanism.
Olsson
Annika
A
Karolinska Institutet, Neonatal Program, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
Kayhan
Gulcin
G
Lagercrantz
Hugo
H
Herlenius
Eric
E
D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D007213:Indomethacin / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D010991:Plethysmography; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D012143:Respiratory Physiological Phenomena
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011453:Prostaglandins; D007213:Indomethacin