**4.4 ARB and inflammation in EAM**

AT1 antagonists are reported to suppress cytokine production and the transcription of cytokine genes in vitro and in vivo (Matsubara, 1998; Siragy, 2000; Carey et al., 2001). ARBs can decrease the expression of IFN-gamma (interferon-gamma), FasL (Fas ligand), iNOS (inducible nitric oxide synthase) and PFP (pore-forming protein) in myocardial tissue, indicating suppression of the activation of infiltrating killer lymphocytes (Seko, 2006). ARB administration downregulates Th1 cytokines (IFN-gamma and IL-2) while upregulating Th2 cytokines (IL-4 and IL-10). Thus, studies of RAS antagonists in inflammatory diseases suggested that Ang II was involved in immune and inflammatory responses and ARBs are useful candidates in preventing the inflammation associated with those disorders. In our lab

Experimental Autoimmune Myocarditis: Role of Renin Angiotensin System 315

Fig. 2. Schematic representation of angiotensin pathway following angiotensin production. Angiotensin II binding to AT1 receptors leads to maintenance of homeostasis in normal physiology whereas pathological stimulation involves major cardiovascular complications. Treatment with ARB can potentially benefit the patients with these complications acting by

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blocking the actions of angiotensin II on AT1 receptors.

**6. References** 

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we have studied the action of ARB against EAM in rats. Out of 10 EAM rats used for treatment with ARB only 20% mortality was observed whereas control group showed 60% mortality. The disease severity was also decreased in the ARB treated group as shown by the less number of apoptotic cells, lesser fibrotic tissue replacement and also low level of inflammatory cellular infiltration when compared with the control group rats (Fig. 1).
