Role of eicosanoids in airflow obstruction and airway plasma exudation induced by trimellitic anhydride-conjugate in guinea-pigs 3 and 8 weeks after sensitization

Trimellitic anhydride (TMA) is a low molecular weight chemical which can cause occupational asthma. We studied the role of eicosanoids in airway responses to TMA at different times after sensitization in actively sensitized guinea-pigs. Sensitization was performed by two intradermal injections of free TMA (0.1 ml of 0.3% TMA in corn oil). At 3 and 8 weeks after sensitization, the guinea-pigs were anaesthetized and challenged with intratracheal instillation of 0.5% TMA conjugated to guinea-pig serum albumin (TMA-GPSA; 50 microliters). Lung resistance (RL) was measured to assess airflow obstruction, and the tissue content of Evans Blue dye was measured to assess airway plasma exudation. Intratracheal instillation of TMA-GPSA induced a slowly progressing increase in RL, reaching a peak at approximately 3.5 min after the challenge (6.0 +/- 2.0 cm H2O/ml/s in the 3-week group and 3.8 +/- 0.6 in the 8-week group). Pretreatment before challenge with pyrilamine (anti-histamine: 2 mg/kg, intravenously) slowed the onset of the increase in RL following challenge with TMA-GPSA, and significantly attenuated the peak response. A combination of pyrilamine and ICI-192,605 (thromboxane receptor antagonist; 0.5 mg/kg, intravenously) completely abolished the increase in RL in both week groups. A combination of pyrilamine and ICI-198,615 (leukotriene C4/D4/E4 receptor antagonist: 0.5 mg/kg, intravenously) did not further attenuate the increase in RL compared with pretreatment with pyrilamine alone, but the induced Evans Blue dye extravasation was completely inhibited in the 3-week group, whereas a remaining extravasation was observed in the 8-week group.(ABSTRACT TRUNCATED AT 250 WORDS)