Tumor necrosis factor alpha (TNFα) potentiates pulmonary chemoreflex responses in anesthetized rats

Abstract

TNFa, a pro‐inflammatory cytokine, is involved in the pathogenesis of asthma and also known for its sensitizing effect on somatic nociceptive afferents. This study was carried out in anesthetized rats to test whether TNFa induces pulmonary C‐fiber hypersensitivity. Before intratracheal (i.t.) instillation of TNFa (~6.8 μg/kg; 1 μg = ~105 units), right atrial injection of a low dose of capsaicin (0.5 μg/kg) elicited a very mild respiratory and cardiovascular depression. Thirty min after the TNFa treatment, the same dose of capsaicin triggered a longer apnea; the apneic ratio (the ratio between apneic duration and average expiratory duration) increased from 180 ± 43% before to 633 ± 67% after TNFa (n = 6; P < 0.005). This sensitizing effect of TNFa gradually declined, but lasted for > 120 min. In contrast, vehicle administered in the same manner did not generate any increase in the responses to capsaicin at the same time point. Moreover, in single‐fiber recording experiments, inhalation of aerosolized TNFa (10 µg/ml; ~0.2 ml) caused a significant increase in the responses to injection of the the same dose of capsaicin. These results suggest that TNFα induces an acute, intense and reversible potentiating effect on the pulmonary chemoreflex to capsaicin, which is probably caused by an increase in the sensitivity of pulmonary C‐fibers. (Supported in part by NIH grant HL58686)