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LPS‐mediated Inflammation Alters Neonatal Central Respiratory Control
Author(s) -
Balan Kannan V,
Kc Prabha,
Mayer Catherine A,
Wilson Christopher G,
Miller Martha J,
Martin Richard J
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.613.12
Subject(s) - lipopolysaccharide , inflammation , carotid body , medicine , proinflammatory cytokine , hypoxia (environmental) , brainstem , respiratory system , endocrinology , hypercapnia , cytokine , lung , chemistry , electrophysiology , organic chemistry , oxygen
Perinatal inflammation is implicated in precipitating lung and brain injury in preterm infants, both of which are associated with impaired respiratory control (IRC). The mechanisms that link peripheral inflammation to central respiratory control have not been well studied. We hypothesized that an endotoxin‐induced inflammatory response in the immature lung triggers cytokine upregulation in the brainstem resulting in IRC. Lipopolysaccharide (LPS, 0.1μg/g) or saline was administered intratracheally into anesthetized vagal‐intact or denervated 10–13 day old F344 rat pups. In experiment 1, 2h post LPS, pups were sacrificed and the brainstem was assessed for mRNA expression of proinflammatory cytokines by RT‐PCR. In experiment 2, the effect of LPS exposure on ventilatory responses (VR) in carotid sinus nerve (CSN) intact and denervated rat pups was quantified using unrestrained whole body plethysmography (WBP). Rat pups exposed to LPS exhibited increased IL‐1β and IL‐6 mRNA and vagotomy decreased IL‐1β mRNA. WBP showed an attenuated VR to hypoxia but not hypercapnia in LPS exposed rat pups. LPS‐instilled CSN denervated pups also showed blunting of the hypoxic response. Our data suggest that pulmonary inflammation during early development and the resulting brainstem cytokine responses are associated with impaired hypoxic VR, which cannot be attributed to altered sensory trafficking from the carotid body. Supported by: HL50527, HL056470