Brown Norway rat asthma model of diphenylmethane-4,4′-diisocyanate (MDI): Impact of vehicle for topical induction

摘要: The development of this Brown Norway (BN) rat asthma model was focused on the duplication at least some hallmarks human diisocyanate using skin as initial priming route exposure. Equal total doses polymeric diphenylmethane-diisocyanate (MDI) were applied to similar surface areas either dissolved in di-n-octyl sebacic acid ester (20%) (SEBA), acetone:olive oil (AOO) or undiluted. elicitation respiratory allergy utilized four repeated nose-only inhalation challenges 30 min with 39 mg/m(3) MDI-aerosol approximately every 2 weeks. Emphasis directed towards analysis responses delayed onset. Endpoints suggestive an allergic inflammatory response examined by bronchoalveolar lavage (BAL) 1 day after last challenge and comprised protein, LDH, cytodifferentiation BAL cells, MCP-1, Th1 Th2 cytokines. MCP-1 cytokines comparatively determined three compartments: fluid, lung-associated lymph nodes (LALN). In all groups sensitized topically MDI typical delayed-onset occurred. lung LALN weights, BAL-protein -LDH significantly increased compared naive control group challenged identically. There compelling evidence a neutrophilic rather than eosinophilic response. patterns interleukin (IL) IL-1alpha, TNF-alpha, IFN-gamma, GM-CSF, IL-4 differed appreciably from one compartment another essentially maximal cells. contrast, same extent compartments measured. Collectively, changes slightly, although consistently more pronounced when SEBA vehicle AOO undiluted MDI. Notable discordance cytokine profiles responses. conclusion, potency administered subsequent asthma-like following exposures appear be dependent multiple factors, them appears associated type matrix used dissolve This animal provides versatile robust experimental tool evaluate assess features MDI-related asthma.