Early and late asthmatic responses to 5'-AMP and ovalbumin inhalation N. Smith and K. J. Broadley. Department of Pharmacology, Welsh School of Pharmacy, Cardiff University, CF10 3XF.	Print Abstract Search PubMed for: Smith N Broadley KJ

Inhalation of antigen in patients with atopic asthma results in an early phase bronchoconstrictor response (EAR), followed in 60% of patients by a late asthmatic response (LAR) (Pepys & Hutchcroft 1975). The LAR is accompanied by increased airway responsiveness to histamine (AHR) (Booj-Noord et al 1971). Inhaled adenosine monophosphate (5'-AMP) causes bronchoconstriction in asthmatics but not in normal subjects (Cushley et al, 1983). Initial reports suggest that it does not cause a LAR (Philips & Holgate 1988) but this has not been investigated in experimental animals. Here we ascertain whether 5'-AMP inhalation causes a LAR in our sensitised guinea-pig model.

MaleDunkin-Hartley guinea-pigs (300-350g) were sensitised with 100µg ovalbumin (OA) and 100mg Al₂OH₃ in 1ml normal saline (i.p.), on days 1 and 5. 12-16 days later, guinea-pigs were challenged with nebulised OA (10µg/ml,1h) or 5'-AMP (3mM or 300mM,1 min). Whole body plethysmography was used to monitor airway function before, and at intervals up to 12h and at 24h post-challenge, recorded as specific airways conductance (sG_aw) (Spruntulis & Broadley 2001). Bronchoalveolar lavage was carried out 24h post-challenge and total and differential cell counts made.

The time course following the OA challenge revealed an EAR, and a LAR at 7h, with mean (n=6) falls in sG_aw of -63.4±2.8% and -22±3.2% respectively. AHR to histamine occurred 24h post-challenge, with a reduction in sG_aw of -30.5±3.4%. A significant increase in total and differential (eosinophils and macrophages) cell counts occurred 24h post-exposure, when compared to saline-challenged animals. Following the 5'-AMP challenges, 3mM produced an EAR and a LAR at 6h, with peak reductions in sG_aw of -40.6±6.2% and -37.3±3.5%, respectively. AHR to histamine occurred 12h post-challenge with a peak reduction in sG_aw of -40.6±6.6%. No bronchoconstriction to histamine occurred 24h pre- or post-challenge, indicating no AHR. A significant infiltration in total cells and macrophages occurred 24h after exposure. Bronchodilation followed the 300mM challenge and a LAR at 6h, with a reduction in sG_aw of -30.5±3.7%. AHR to histamine occurred 12h after challenge, the peak reduction in sG_aw being -32.0±1.7%. No AHR occurred 24h post-challenge. A significant increase in total and differential cell counts occurred 24h post-exposure.

In conclusion, an OA challenge can reproducibly reveal an EAR, LAR, cellular infiltration and AHR in our animal model. This study has demonstrated for the first time that a late asthmatic response and airway hyperreactivity to histamine can be revealed following a 5'-AMP challenge in a sensitised guinea-pig model of asthma. Cellular infiltration occurring 24h after challenge suggests that it may be associated with the LAR and AHR.

Supported by a GlaxoSmithKline studentship to N.S.

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