Recovery rates from acute and chronic ovalbumin challenge in guinea pigs

Rhys L. Evans, William R. Ford, Emma J. Kidd and Kenneth J. Broadley. Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, Cathays Park, Cardiff CF10 3XF, UK

Challenging guinea pigs with acute or chronic antigen exposures causes early (EAR) and late asthmatic responses (LAR), airway hyperreactivity (AHR) and inflammatory cell influx into the airways (Smith et al., 2007), features that are commonly associated with asthma. This study examined the rate of recovery of AHR and airways inflammation following acute and chronic ovalbumin challenge of sensitised guinea pigs.

Groups of six, male Dunkin-Hartley guinea pigs (200-250g) were sensitised with 100μg ovalbumin (OA) and 100mg aluminium hydroxide in 1ml of pathogen-free saline on days 1 and 5. On day 15, acute and chronic groups were exposed to aerosolised 0.01% OA or saline for 60mins. For the chronic studies, exposure to 0.1% OA, with 30mg/kg mepyramine, or saline then occurred every 48 hours until day 29. On day 31, the chronic OA group was exposed to 0.1% OA minus mepyramine and the chronic saline group was exposed to saline. EAR and LAR were measured using a plethysmograph that gave values of specific airway conductance (sGaw). Airway hyperreactivity was determined by exposing the guinea pigs to histamine (20s, 1mM) on day 14 and either 24 or 72h post-final exposure and recording values of sGaw. Total and differential cell counts in bronchoalveolar lavage fluid were then carried out at either 24 or 72h post-final exposure, immediately following the final histamine inhalation.

Figure 1: Cathinone effect with 5-HT7 and/or α2 antagonists

Acute OA and chronic OA challenges both induced EAR (sGaw = -68.0±5.1%; -60.6±5.5%, respectively) and LAR (sGaw = -22.3±3.9%; -19.9±2.8%, respectively). Guinea pigs solely exposed to saline did not demonstrate EAR or LAR. No groups responded to histamine pre-exposure. Acute OA-challenged guinea pigs were hyperreactive 24h post-exposure (sGaw = -27.5±4.5%) but this hyperreactivity had disappeared by 72h (sGaw = -0.2±2.7%). Chronic OA-challenged guinea pigs were hyperreactive both 24h (sGaw = -31.0±5.6%) and 72h post-exposure (sGaw = -25.4±7.1%). Acute (2.5±0.1x106 cells ml-1) or chronic (2.2±0.1 x106 cells ml-1) exposure to saline did not increase total cellular influx compared to naïve guinea pigs (1.5±0.1x106 cells ml-1). An increase was observed in acute OA-challenged guinea pigs after 24h (8.8±0.6x106 cells ml-1) but at 72h post-exposure (3.3±0.2x106 cells ml-1) the leukocyte levels were not significantly different from naïve guinea pigs. The greatest cellular influx compared to other groups was seen in chronic OA-challenged guinea pigs after 24h (1.5±0.06x107 cells ml-1). At 72h levels were reduced (6.8±0.7x106 cells ml-1) but were still significantly greater than in naïve guinea pigs.

Both the acute and chronic OA challenge models exhibit four of the main features associated with atopic asthma. However, after 72 hours the acute model had recovered to a normal level of reactivity and leukocyte number. This was not the case for the chronic model, suggesting remodelling of the airways had occurred and therefore the chronic model appears to more closely resemble human asthma.

Supported by a studentship from BBSRC & GSK. We thank Dr. Tony Nials for helpful advice.

SMITH, N and BROADLEY, K. J. (2007). International Immunopharmacology, 7, 183-190