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In vivo pharmacological evaluation of compound 48/80-induced airways oedema by MRI
H Karmouty-Quintana1, F-X Blé, C Cannet
1Global Imaging Group, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Background And Purpose:
Allergen-induced airways oedema in actively sensitized rats has been studied earlier by magnetic resonance imaging (MRI). We used MRI to follow the consequences of non-immunological mast cell activation induced by compound 48/80 in the rat lungs in vivo.
Experimental Approach:
Male naïve rats were scanned by MRI prior to and at several time points following intratracheal administration of the mast cell secretagogue, compound 48/80. The effects of a range of drugs on the response induced by compound 48/80 were studied.
Key Results:
Strong fluid signals were detected by MRI in the lungs at 24 h after compound 48/80, correlating with increased protein concentration and inflammatory cell infiltration in bronchoalveolar lavage, and with perivascular oedema observed histologically. Pharmacological intervention demonstrated that the increase in MRI signal volume induced by compound 48/80 24 h after challenge was blocked by disodium cromoglycate and the glucocorticoid, budesonide. Pretreatment with wortmannin, capsazepine, DNK333 (a dual neurokinin (NK) 1 and NK2 antagonist) or the anti-allergy drug CGS8515, but not indomethacin, resulted in partial inhibition.
Conclusions And Implications:
Compound 48/80 induced a complex inflammatory reaction which did not solely involve mast cell degranulation but also activation of sensory nerves and was qualitatively similar to allergen challenge. Changes observed by MRI correlated with decreases in protein concentration in BAL fluid. However, the magnitude of the changes detected was greater using MRI. Our results demonstrate that MRI is a sensitive and efficient tool to assess the effects of drugs on lung inflammation.
Insights
Magnetic resonance imaging (MRI) effectively visualized lung inflammation in rats following mast cell activation. This sensitive imaging technique can assess drug efficacy in treating lung inflammation, showing complex reactions beyond mast cell degranulation.
Area of Science:
- Pulmonary Medicine
- Medical Imaging
- Pharmacology
Background:
- Allergen-induced airway edema in rats has been previously studied using MRI.
- Non-immunological mast cell activation via compound 48/80 in rat lungs was investigated in vivo.
Purpose of the Study:
- To utilize MRI to monitor lung inflammation following mast cell activation by compound 48/80.
- To evaluate the efficacy of various drugs in modulating the compound 48/80-induced lung response.
Main Methods:
- Male rats underwent MRI scanning before and after intratracheal administration of compound 48/80.
- The effects of pharmacological agents on compound 48/80-induced lung changes were assessed.
Main Results:
- MRI detected significant fluid signals in rat lungs 24 hours post-compound 48/80 administration.
- These signals correlated with increased protein concentration, inflammatory cells, and perivascular edema.
- Disodium cromoglycate and budesonide blocked the MRI signal increase, while other agents showed partial inhibition.
Conclusions:
- Compound 48/80 triggers a complex inflammatory response involving mast cells and sensory nerves, similar to allergen challenge.
- MRI is a sensitive tool for assessing drug effects on lung inflammation, detecting changes more accurately than protein concentration analysis.
