1. β2-Adrenergic Agonists Suppress Rat Autoimmune Myocarditis
by Mototsugu Nishii, Takayuki Inomata, Hiroe Niwano, Hitoshi Takehana, Ichiro Takeuchi, Hironari Nakano, Hisahito Shinagawa, Takashi Naruke, Toshimi Koitabashi, Jun-ichi Nakahata, and Tohru Izumi
Circulation
Volume 114(9):
August 29, 2006
Copyright © American Heart Association, Inc. All rights reserved.

2. Figure 1. Histological findings in EAM hearts on day 21 of in vivo administration of β-AR agents.
Figure 1. Histological findings in EAM hearts on day 21 of in vivo administration of β-AR agents. Administration of propranolol at 10 mg/kg (A) facilitated interstitial cellular infiltration compared with that of metoprolol at 30 mg/kg (B) or vehicle (C). Conversely, administration of either formoterol at 22.5 μg/kg (D) or salbutamol at 200 μg/kg ameliorated interstitial cellular infiltration (E). Bars=1 mm or 250 μm (thick, for ×1; thin, for ×40, respectively).
Mototsugu Nishii et al. Circulation. 2006;114:
Copyright © American Heart Association, Inc. All rights reserved.

3. Figure 2. Microscopic findings in EAM rats treated with formoterol at 22.5 μg/kg, salbutamol at 200 μg/kg, or vehicle from days 14 to 21. β2-AR agonists reduced interstitial cellular infiltration and destruction of myocardial fibers compared with the vehicle.
Figure 2. Microscopic findings in EAM rats treated with formoterol at 22.5 μg/kg, salbutamol at 200 μg/kg, or vehicle from days 14 to 21. β2-AR agonists reduced interstitial cellular infiltration and destruction of myocardial fibers compared with the vehicle. Bars=250 μm (thin, for ×100).
Mototsugu Nishii et al. Circulation. 2006;114:
Copyright © American Heart Association, Inc. All rights reserved.

4. Figure 3. Effects of β-AR agonists on myocarditogenic T lymphocytes stimulated by specific antigen and antigen-presenting cells.
Figure 3. Effects of β-AR agonists on myocarditogenic T lymphocytes stimulated by specific antigen and antigen-presenting cells. Cell proliferation (A) and production of IL-12 (B) and IFN-γ (C) in the culture supernatant were determined by 3H-thymidine uptake and an ELISA kit. Three series of experiments were performed for each investigation. Error bars represent SEM. β-AR agonists decreased cell proliferation and production of IL-12 and IFN-γ (*P< vs culture with vehicle only), and inhibitory effects by formoterol and salbutamol were very much stronger compared with denopamine in each concentration (P<0.0001).
Mototsugu Nishii et al. Circulation. 2006;114:
Copyright © American Heart Association, Inc. All rights reserved.

5. Figure 4. ICI118,551 reversed the inhibitory effect of β2-AR stimulation on the production of Th1-cytokines.
Figure 4. ICI118,551 reversed the inhibitory effect of β2-AR stimulation on the production of Th1-cytokines. Levels of IL-12 and IFN-γ in the culture supernatant were determined by an ELISA kit. Three series of experiments were performed for each investigation. Error bars represent SEM. *P< vs culture with the vehicle only; #P< vs each concentration of formoterol without ICI118,551.
Mototsugu Nishii et al. Circulation. 2006;114:
Copyright © American Heart Association, Inc. All rights reserved.

6. Figure 5. The proliferation of T lymphocytes and levels of IL-12, IFN-γ, and intracellular cAMP in cardiac myosin–primed lymph nodes from EAM rats treated with β-AR agent or vehicle.
Figure 5. The proliferation of T lymphocytes and levels of IL-12, IFN-γ, and intracellular cAMP in cardiac myosin–primed lymph nodes from EAM rats treated with β-AR agent or vehicle. Cell proliferation, levels of Th1-cytokines, and levels of intracellular cAMP were determined by measuring radioactivity of incorporated 3H-thymidine and an ELISA kit. Each group contained 9 rats. Closed circle indicates individual data; open circle and error bar, mean±SEM for each group. No significant difference was shown in comparisons of metoprolol and vehicle groups.
Mototsugu Nishii et al. Circulation. 2006;114:
Copyright © American Heart Association, Inc. All rights reserved.