Airway inflammation and central respiratory control: Results from in vivo and in vitro neonatal rat

In infants, respiratory infection elicits tachypnea. To begin to evaluate the role of brainstem cytokine expression in modulation of breathing pattern changes, we compared the pattern generated after endotracheal instillation of lipopolysaccharide (LPS) in in vivo rat pups to local pro-inflammatory cytokine injection in the nucleus tractus solitarius (nTS) in an in vitro en bloc brainstem spinal cord preparation. We hypothesized that both challenges would elicit similar changes in patterning of respiration. In anesthetized, spontaneously breathing rat pups, lipopolysaccharide (LPS) or saline was instilled in the airway of urethane-anesthetized rats (postnatal days 10-11). We recorded diaphragm EMG over the subsequent 2 h and saw a 20-30% decrease in interburst interval (Te) at 20-80 min post-injection in LPS-instilled animals with no significant change in Ti. In contrast, IL-1 beta injections into the nTS of en bloc in vitro brainstem-spinal cord preparations from 0 to 5 day-old pups maintained Ti and caused an increase in Teas early as 20 mm later, decreasing frequency for 80-120 min after injection. Our results suggest that the neonatal respiratory response to the cytokine IL-1 beta mediated inflammatory response depends on the site of the inflammatory stimulus and that the direct effect of IL-1 beta in the nTS is to slow rather than increase rate. (C) 2011 Elsevier B.V. All rights reserved.