Leukotriene B(4), administered via intracerebroventricular injection, attenuates the antigen-induced asthmatic response in sensitized guinea pigs

BACKGROUND: Despite intensive studies focused on the pathophysiology of asthmatic inflammation, little is known about how cross-talk between neuroendocrine and immune systems regulates the inflammatory response during an asthmatic attack. We recently showed corresponding changes of cytokines and leukotriene B(4 )(LTB(4)) in brain and lung tissues of antigen-challenged asthmatic rats. Here, we investigated how LTB(4 )interacts with the neuroendocrine-immune system in regulating antigen-induced asthmatic responses in sensitized guinea pigs. METHODS: Ovalbumin-sensitized guinea pigs were challenged by inhalation of antigen. Vehicle, LTB(4 )or U75302 (a selective LTB(4 )BLT1 receptor inhibitor) was given via intracerebroventricular injection (i.c.v.) 30 min before challenge. Airway contraction response was evaluated using Penh values before and after antigen challenge. The inflammatory response in lung tissue was evaluated 24 h after challenge. The LTB(4 )content of lung and brain homogenate preparations was detected by reversed phase high-performance liquid chromatography (RP-HPLC). Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using ELISA kits. RESULTS: Antigen challenge impaired pulmonary function and increased inflammatory cell infiltration in lung tissue. These responses could be significantly suppressed by LTB(4), 30 ng i.c.v., in ovalbumin-sensitized guinea pigs. LTB(4 )content of lung and brain homogenates from antigen-challenged guinea pigs was significantly increased. In addition, administration of LTB(4 )via i.c.v. markedly increased CORT and ACTH level in plasma before antigen challenge, and there were further increases in CORT and ACTH levels in plasma after antigen challenge. U75302, 100 ng i.c.v., completely blocked the effects of LTB(4). In addition, U75302, 100 ng via i.c.v. injection, markedly decreased LTB(4 )content in lung homogenates, but not in brain homogenates. CONCLUSIONS: Increased LTB(4 )levels in brain during asthmatic attacks down-regulates airway contraction response and inflammation through the BLT1 receptor. Stimulation of the hypothalamic-pituitary-adrenal axis by LTB(4 )may result in an increase in systemic glucocorticoids which, in turn, would feed back to suppress the asthmatic response.