Effect of immunosuppressive drugs on cytokine production in canine whole blood stimulated with lipopolysaccharide or a combination of ionomycin and phorbol 12-myristate 13-acetate
AuthorDandrieux, JRS; Narayanan, L; Firestone, S; Archer, TM; Mansfield, CS
Source TitleVeterinary Medicine and Science
PublisherJohn Wiley & Sons
University of Melbourne Author/sDandrieux, Julien; Mansfield, Caroline; Dandrieux, Julien; Firestone, Simon
AffiliationVeterinary and Agricultural Sciences
Melbourne Veterinary School
Veterinary Clinical Sciences
Document TypeJournal Article
CitationsDandrieux, J. R. S., Narayanan, L., Firestone, S., Archer, T. M. & Mansfield, C. S. (2019). Effect of immunosuppressive drugs on cytokine production in canine whole blood stimulated with lipopolysaccharide or a combination of ionomycin and phorbol 12-myristate 13-acetate. Veterinary Medicine and Science, 5 (2), pp.199-205. https://doi.org/10.1002/vms3.143.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498811
A pharmacodynamic assay has been previously developed to monitor ciclosporin treatment in dogs by assessing inhibition of cytokine transcription after whole blood stimulation with 12-myristate 13-1 acetate and ionomycin (PMA/I). In this study, whole blood stimulation with either PMA/I or lipopolysaccharide (LPS) was used to assess the effect of multiple drugs (azathioprine, ciclosporin, mycophenolate, leflunomide and prednisone) after a 7-day treatment course on production of cytokines measured with a multiplex assay in healthy dogs (n = 4 for each treatment). Interleukin-10 (IL-10), interferon gamma (IFN?) and tumour necrosis factor alpha (TNFa) were significantly activated by PMA/I stimulation and IL-6, IL-10 and TNFa by LPS stimulation, in the absence of immunosuppressive drugs. After ciclosporin treatment, IL-10, IFN? and TNFa production was significantly reduced after stimulation with PMA/I compared to pre-treatment. After prednisone treatment, TNFa production was significantly reduced after stimulation with PMA/I or LPS compared to pre-treatment. No significant change was observed after treatment with azathioprine, leflunomide or mycophenolate. This methodology may be useful to monitor dogs not only treated with ciclosporin, but also with prednisone or a combination of both. Further studies are needed to assess the use of this assay in a clinical setting.
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