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Exacerbation of autoimmune myocarditis by an immune checkpoint inhibitor is dependent on its time of administration in mice

Tsuruoka, K;Wakabayashi, S;Morihara, H;Matsunaga, N;Fujisaka, Y;Goto, I;Imagawa, A;Asahi, M;

Severe EAM developed in 3weeks; wide inflammatory lesions were observed in the cardiac sections. Furthermore, inflammatory/fibrotic genes, such as interleukin 1, interleukin 6, and collagen 1, were upregulated, although the cardiac function was not significantly affected. The subsequent administration of mPD1ab at 2weeks post administration of the first MyHC- fragment exacerbated EAM, whereas the administration of mPD1ab concurrent with MyHC- fragment administration did not exacerbate EAM. The subsequent administration of mPD1ab significantly increased the infiltration of cluster of differentiation (CD)4- and F4/80-positive cells, whereas the concurrent administration of mPD1ab significantly decreased the infiltration of CD4-positive cells, indicating that the concurrent and subsequent administration of mPD1ab had opposite effects on immune/inflammatory cell infiltration.