54 - THE EFFECT OF SYK INHIBITOR ON KAWASAKI DISEASE-LIKE MURINE VASCULITIS. - THE RELATION BETWEEN SERUM CYTOKINES AND DEVELOPMENT OF VASCULITIS -

[Background] Activation of molecules of the innate immune system including Syk is involved in the development of KD-like murine vasculitis which is induced by Candida albicans water-soluble fraction (CAWS). Previously, we reported that Syk inhibitor suppressed the development of vasculitis in the aortic annulus area of this model. In this study, we clarified the changes over time of the vasculitis and of serum cytokines level, and the influence of Syk inhibitor on this model.
[Materials/Methods] CAWS were intraperitoneally injected to mice for 5 consecutive days, and Syk inhibitor or solvent were intraperitoneally administered once a day from the day after the final CAWS-injection. The day that started CAWS-injection was set as day 1. Collection of blood from the hearts and sampling the hearts was performed on day 0, 1, 3, 5, 6, 12, and 26. Serial sections of the hearts were made, and the histological severity of the vasculitis was assessed. Then, serum cytokines level was measured. The severity of inflammation was classified into 4 grades: Grade 0, no inflammation; Grade 1, inflammatory cell infiltration limited to one layer (intima, media or adventitia); Grade 2, inflammatory cell infiltration limited to 2 layers; and Grade 3, inflammatory cell infiltration involving 3 layers.
[Results] After CAWS-injection, some animals were observed to develop tiny grade 3 lesions on day 6. Grade 1 lesions were localized to intima, and grade 2 lesions were localized to the intima and adventitia. As for cytokines, IL-5, IL-6, INFγ, TNF-α, and KC/GRO increased by day 6, and IL-1β, IL-2, IL-10, and KC/GRO increased after day 6. Syk inhibitor completely suppressed the development of panvasculitis in the aortic annulus area, and suppressed the increase of the aforementioned cytokines.
[Conclusion] Inflammatory cell infiltration was thought to start from the intima, progress to the adventitia, and then to the media. On day 6, initiation of panvasculitis was observed. Syk inhibitor-treatment from the early stage of vasculitis suppressed the subsequent progression of inflammation. Cytokines that rise promptly with CAWS-injection may be involved in the pathogenesis of vasculitis, and cytokines that rise late after CAWS-injection may be involved in the progression of vasculitis, and both were suppressed by Syk inhibitor-treatment.