Abstract-Angiotensin II type 2 (AT 2 ) receptors can be regarded as an endogenous repair system, because the AT 2 receptor is upregulated in tissue damage and mediates tissue protection. A potential therapeutic use of this system has only recently come within reach through synthesis of the first selective, orally active, nonpeptide AT 2 receptor agonist, compound 21 (C21; dissociation constant for AT 2 receptor: 0.4 nM; dissociation constant for angiotensin II type 1 receptor: Ͼ10 000 nM). This study tested AT 2 receptor stimulation with C21 as a potential future therapeutic approach for the inhibition of proinflammatory cytokines and of nuclear factor B. C21 dose-dependently (1 nM to 1 mol/L) reduced tumor necrosis factor-␣-induced interleukin 6 levels in primary human and murine dermal fibroblasts. AT 2 receptor specificity was controlled for by inhibition with the AT 2 receptor antagonist PD123319 and by the absence of effects in AT 2 receptor-deficient cells. AT 2 receptor-coupled signaling leading to reduced interleukin 6 levels involved inhibition of nuclear factor B, activation of protein phosphatases, and synthesis of epoxyeicosatrienoic acid. Inhibition of interleukin 6 promoter activity by C21 was comparable in strength to inhibition by hydrocortisone. C21 also reduced monocyte chemoattractant protein 1 and tumor necrosis factor-␣ in vitro and in bleomycin-induced toxic cutaneous inflammation in vivo. This study is the first to show the anti-inflammatory effects of direct AT 2 receptor stimulation in vitro and in vivo by the orally active, nonpeptide AT 2 receptor agonist C21. These data suggest that pharmacological AT 2 receptor stimulation may be an orally applicable future therapeutic approach in pathological settings requiring the reduction of interleukin 6 or inhibition of nuclear factor B. (Hypertension. 2010;55:924-931.)

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Paecilomyces lilacinus is a rare cause of contact lens-associated keratitis. The infection is difficult to eradicate because of multiple antifungal drug resistance and has a poor outcome. A female patient developed contact lens-associated keratitis and Paecilomyces lilacinus could be demonstrated in the corneal abrasion. Despite antifungal therapy with voriconazole a keratoplasty à chaud was necessary and a poor final visual acuity could not be avoided.