Temporal expression of inflammatory mediators in brain basilar artery vasculitis and cerebrospinal fluid of rabbits with coccidioidal meningitis

• Published in: Clinical and experimental immunology Vol. 143; no. 3; pp. 458 - 466
• Main Authors: Zucker, K. E., Kamberi, P., Sobel, R. A., Cloud, G., Meli, D. N., Clemons, K. V., Stevens, D. A., Williams, P. L., Leib, S. L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2006; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Animal Studies; Animals; Basilar Artery - metabolism; Basilar Artery - pathology; Biological and medical sciences; Brain - microbiology; Coccidioides - isolation & purification; Coccidioides immitis; coccidioidomycosis; Coccidioidomycosis - cerebrospinal fluid; Coccidioidomycosis - metabolism; Coccidioidomycosis - pathology; Cytokines - biosynthesis; Cytokines - cerebrospinal fluid; Cytokines - genetics; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunopathology; Inflammation Mediators - metabolism; inflammatory mediators; Male; Matrix Metalloproteinase 9 - biosynthesis; Matrix Metalloproteinase 9 - cerebrospinal fluid; Matrix Metalloproteinase 9 - genetics; Medical sciences; meningitis; Meningitis, Fungal - cerebrospinal fluid; Meningitis, Fungal - metabolism; Meningitis, Fungal - pathology; mRNA; Rabbits; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; Spinal Cord - microbiology; Up-Regulation - immunology; vasculitis; Vasculitis, Central Nervous System - metabolism; Vasculitis, Central Nervous System - pathology; Mycosis; Central nervous system; Rabbit; Cardiovascular disease; mRNA; Cerebrospinal fluid; Encephalon; Vascular disease; Immunology; Messenger RNA; Vasculitis; Coccidioidomycosis; Meningitis; Immunopathology; Nervous system diseases; Basilar artery; Inflammation; Lagomorpha; Infection; inflammatory mediators; Vertebrata; Mammalia; Animal; Central nervous system disease; Mediator; Circulatory system
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2006.03011.x

Summary
Strokes due to transmural vasculitis associated with coccidioidal meningitis result in significant morbidity and mortality. The immunological and inflammatory processes responsible are poorly understood. To determine the inflammatory mediators, i.e. cytokines, chemokines, iNOS, matrix metalloproteinase‐9 (MMP‐9), that possibly contribute to vasculitis, temporal mRNA expression in brain basilar artery samples and MMP‐9 protein in the CSF of male NZW rabbits infected intracisternally with 6·5 × 104 arthroconidia of Coccidioides immitis were assessed. Five infected and 3 sham‐injected rabbits at each time point were euthanized 4, 9, 14 and 20 days post infection. All infected rabbits had neurological abnormalities and severe vasculitis in the basilar arteries on days 9–20. In basilar arteries of infected animals versus controls, mRNAs encoding for IL‐6, iNOS, IFN‐γ, IL‐2, MCP‐1, IL‐1β, IL‐10, TNF‐α, CCR‐1, MMP‐9, TGF‐β, as well as MMP‐9 protein in CSF, were found to be significantly up‐regulated. Thus, this study identified inflammatory mediators associated with CNS vasculitis and meningitis due to C. immitis infection. Assessment of the individual contribution of each mediator to vasculitis may offer novel approaches to the treatment of coccidioidal CNS infection. This study also provides unique methodology for immunology studies in a rabbit model.