U75302 Blocked The Ltb <sub> 4 </ Sub> Role In The Regulation Of The Guinea Pig Asthmatic Reaction

Objective:Lately investigation in our lab showed the Correlative changes of interferon-gamma and interleukin-4 between cortical layer and pulmonary airway of sensitized rats. External LTB₄ (icv) inhibited the decline of lung function and the aggregation of leucocytes in the lung tissue. All these results suggests that LTB₄, the metabolite of 5-LO pathway in CNS, can play a role of Neuroimmunomodulation. To investigate the regulatory effects of leukotriene B₄ (LTB₄) , we use guinea pig asthmatic model and U75302 the antagonist of LTB₄ for the first time. Methods:Each guinea pig was sensitized by 1ml 1% Ovalbumin(OVA) solution (ip) and 0.5ml ×2 1%OVA solution (im). Twenty one days later, a stainless steel cannulae was inserted into the lateral ventricle. The pulmonary function was observed after the antigen challenging on the conscious OVA-sensitized guinea pigs, LTB₄ was icv 30min before and its antagonist U75302 was icv 35min before. We use Penh to evaluate the bronchoconstriction. Then the brain and lung sample were taken from the anesthetized guinea pigs, the contents of LTB₄ were measured by HPLC. The inflammatory cells in the BALF were counted. Results:1. After the antigen challenged, the respiratory frequency, tidal volume and Penh value of OVA-sensitized guinea pigs increased compared with NS control group. The number of inflammatory cells in BALF in antigen challenged group was significantlyhigher than that in control group. The contents of LTB4 in lung and brain homogenates were both increased significantly.2. OVA-sensitized guinea pigs LTB4 30ng icv without antigen challenging, whose respiratory frequency, tidal volume and Penh value have no significant changes compared to control group.3. OVA-sensitized guinea pigs U75302 lOOng icv without antigen challenging, whose respiratory frequency, tidal volume and Penh value have no significant changes compared to control group.4. LTB4 30ng icv ,before the antigen challenging on sensitized guinea pigs, inhibit the increase in tidal volume, Penh value, and amount of inflammatory cells in BALF calls by antigen challenging. At the same time , the contents of LTB4 in lung and brain homogenates were both decreased significantly.5. LTB4 antagonist U75302 lOOng icv , before the antigen challenging on sensitized guinea pigs, have no effect on the increase in tidal volume, Penh value, and amount of inflammatory cells in BALF calls by antigen challenging.6. LTB4 antagonist U75302 lOOng icv , before LTB4 30ng was injected, and then challenged with OVA, the Penh value of sensitized guinea pigs increased compared with LTB4 30ng group, the number of inflammatory cells in BALF also increased significantly. The contents of LTB4 in lung homogenates increased significantly, on the contrary which in brain homogenates decreased. Conclusion:1. OVA challenging cause increase of airway resistance, aggregation ofinflammatory cells in airway, and LTB4 content in lung and brain increased too.2. Extensive LTB4 icv can inhibit the increase of airway resisitance, aggregation of inflammatory cells in airway and LTB4 level in lung and brain homogenates3. U75302 icv before LTB4 can block the inhibitory effect of LTB4 on the increase of airway resistance, aggregation of inflammatory cells in airway and LTB4 pontent in lung caused by antigen challenging, but the increase of LTB4 content in brain has no change.4. All results above indicated that the increase of LTB4 level in brain may be related with the neuro-endocrine-immunomodulatory effect in brain, which form a regulatory effect to symptom and sign of asthma.