Involvement of inflammatory mediators in the airway responses to trimellitic anhydride in sensitized guinea‐pigs

Abstract

1 We examined the effect of various pharmacological agents on the acute bronchoconstrictor response and airway microvascular leakage in a model of guinea-pig sensitization to trimellitic anhydride (TMA) a cause of low molecular weight occupational asthma in man. 2 Guinea-pigs were given intradermal injections of 0.1 ml of 0.3% TMA in corn oil; 21-28 days later, anaesthetized guinea-pigs were challenged with TMA conjugated to guinea-pig albumin by tracheal instillation. Changes in lung resistance were measured and airway microvascular leakage was quantified by measuring the extravasation of Evans blue dye into the airway tissue.3 Sensitized guinea-pig (n = 9 in each group) were pretreated with chlorpheniramine (2.5 mg kg-', i.v.), WEB 2086 (10 ±g kg-', i.v.), BW 4AC (50mg kg-', i.p.), nedocromil sodium (2% aerosol for 60 s) or vehicle alone. 4 Pretreatment with chlorpheniramine inhibited both the acute bronchoconstrictor response and the increase in airway microvascular leakage. WEB 2086 and nedocromil sodium partially inhibited the bronchoconstrictor response but had no significant effect on airway microvascular leakage. BW 4AC caused a non-significant reduction of the bronchoconstrictor response and airway microvascular leakage. 5 These results indicate that both the bronchoconstrictor response and the airway microvascular response in this model of sensitization is mediated to a large extent by histamine. PAF but not 5-lipoxygenase products also partially mediates the bronchoconstrictor response but not the airway microvascular leakage. Nedocromil sodium partially inhibits the bronchoconstrictor response only.

Trimellitic Anhydride-Induced Cellular Infiltration into Guinea Pig Lung Varies with Age but Not Gender

“…Guinea pigs sensitized by intradermal injection of TMA in corn oil and challenged by intratracheal instillation of TMA conjugated to guinea pig serum albumin (TMA-GPSA) respond with immediate bronchoconstriction, microvascular leakage of proteins and infiltration of inflammatory cells into the lung, including significant eosinophilia. These and other studies of TMA-induced respiratory disease in the guinea pig have used Hartley or Dunkin-Hartley guinea pigs weighing approximately 300 g (estimated age of 21–28 days) at the time of sensitization [see 5, 6, 7, 8, 9, 10]. Guinea pigs this size are not yet sexually mature, but have been used to study effects of an occupational allergen where exposure to adults is of primary concern.…”