Lung and brainstem cytokine levels are associated with breathing pattern changes in a rodent model of acute lung injury

Acute lung injury evokes a pulmonary inflammatory response and changes in the breathing pattern. The inflammatory response has a centrally mediated component which depends on the vagi. We hypothesize that the central inflammatory response, complimentary to the pulmonary inflammatory response, is expressed in the nuclei tractus solitarii (nTS) and that the expression of cytokines in the nTS is associated with breathing pattern changes. Adult, male Sprague-Dawley rats (n = 12) received intratracheal instillation of either bleomycin (3 units in 120 μl of saline) or saline (120 μl). Respiratory pattern changed by 24 h. At 48 h, bronchoalveolar lavage fluid and lung tissue had increased IL-1β and TNF-α levels, but not IL-6. No changes in these cytokines were noted in serum. Immunocytochemical analysis of the brainstem indicated increased expression of IL-1β in the nTS commissural subnucleus that was localized to neurons. We conclude that breathing pattern changes in acute lung injury were associated with increased levels of IL-1β in brainstem areas which integrate cardio-respiratory sensory input.