Intratracheal LPS administration attenuates the acute hypoxic ventilatory response: Role of brainstem IL-1β receptors.
Perinatal inflammation and infection are commonly associated with various respiratory morbidities in preterm infants including apnea of prematurity. In this study, we investigated whether pulmonary inflammation via intra-tracheal micro-injection of lipopolysaccharide (LPS) into neonatal rats modifies respiratory neural control via an IL-1β receptor-dependent mechanism. Prior to an intra-tracheal micro-injection of LPS (1mg/kg), 10day old (Postnatal age, P10) rats received an intraperitoneal (i.p.) or intracisternal (i.c.) micro-injection of the IL-1β receptor antagonist AF12198. Whole-body plethysmography was performed two hours later to assess the magnitude of the acute hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses. Intra-tracheal LPS dose-dependently attenuated the acute HVR compared to saline (control) treated rats, whereas the HCVR was not affected. Pre-treatment with an i.c. (but not i.p.) micro-injection of AF12198 15min prior to LPS prevented the attenuated HVR. These data indicate that intrapulmonary inflammation affects brainstem respiratory neural pathways mediating the ventilatory response to acute hypoxia via an IL-1β-dependent pathway. These findings are relevant to our understanding of the way that pulmonary inflammation may affect central neural mechanisms of respiratory insufficiency commonly seen in preterm infants.
Department of Pediatrics, Case Western Reserve University, Rainbow Babies & Children's Hospital, Cleveland, OH, 44106, USA.
A P
AP
Ribeiro
Department of Pediatrics, Case Western Reserve University, Rainbow Babies & Children's Hospital, Cleveland, OH, 44106, USA.
C A
CA
Mayer
Department of Pediatrics, Case Western Reserve University, Rainbow Babies & Children's Hospital, Cleveland, OH, 44106, USA.
C G
CG
Wilson
Department of Pediatrics, Case Western Reserve University, Rainbow Babies & Children's Hospital, Cleveland, OH, 44106, USA.
R J
RJ
Martin
Department of Pediatrics, Case Western Reserve University, Rainbow Babies & Children's Hospital, Cleveland, OH, 44106, USA. Electronic address: pmm71@case.edu.
P M
PM
MacFarlane
D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects / Q000276:immunology*; D002491:Central Nervous System Agents / Q000494:pharmacology; D004926:Escherichia coli; D006935:Hypercapnia / Q000276:immunology; D000860:Hypoxia / Q000276:immunology*; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D008845:Microinjections; D009434:Neural Pathways / Q000187:drug effects / Q000276:immunology; D010991:Plethysmography; D011014:Pneumonia / Q000276:immunology*; D011506:Proteins / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012119:Respiration; D014132:Trachea
C102533:AF 12198; D002491:Central Nervous System Agents; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011506:Proteins; D017472:Receptors, Interleukin-1
Control of breathing; Hypoxia; IL-1β; Inflammation; Lipopolysaccharide