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BACKGROUND AND AIMS: CD40-CD40L interactions appear to play an important role in the pathogenesis of experimental colitis. We tested the effect and investigated the underlying mechanism of action of systemically administered antisense oligonucleotide (ASO) targeting CD40 formulated in amphoteric liposomes (nov038/CD40). The charge characteristics of the amphoteric liposomes (anionic surface charge at physiological pH that becomes cationic at low pH), facilitate efficient sequestration of the ASO inside the liposomes at low pH and the direction of the carriers towards macrophages and dendritic cells under physiological conditions. METHODS: Colitis was induced in Balb/c mice using 2,4,6-Trinitrobenzene sulphonic acid (TNBS) and treated with nov038/CD40. Disease was monitored by body weight, histology, cytokine profiling and changes in immune cell populations. CD40 expression on different cell subsets was analyzed by flow cytometry. An antigen challenge model was used to determine neoimmunity under CD40 modulation. RESULTS: Administration of nov038/CD40 inhibited the development of TNBS colitis as assessed by weight loss, histology and cytokine profiles; unformulated CD40 ASO or nov038 encapsulating an unrelated ASO (nov038/SCR) were ineffective. The novel agent is potent as it completely suppressed even established colitis with a single treatment and significantly reduced T-cell activation as well as levels of pro-inflammatory mediators in serum. The inhibition of CD40 specifically occurred in macrophages, but not in B-cells. In contrast to prednisolone, standard treatment for inflammatory bowel diseases (IBD) that is effective in a single administration and involves extensive immunosuppression, nov038/CD40 did not affect the number of B- or Treg cells. Eventually, we observed a largely intact neoimmunity under conditions of a CD40 inhibition. CONCLUSIONS: Administration of nov038/CD40, but neither naked CD40 ASO nor nov038/SCR, prevents the development and treats established colitis in mice. Delivery of CD40 ASO in nov038 is highly cell-specific as it selectively suppresses CD40 on macrophages, but not on B-cells; the novel agent has strong anti-inflammatory characteristics without being immunosuppressive.

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Sinupret(®), a herbal medicinal product made from Gentian root, Primula flower, Elder flower, Sorrel herb, and Verbena herb is frequently used in the treatment of acute and chronic rhinosinusitis and respiratory viral infections such as common cold. To date little is known about its potential antiviral activity. Therefore experiments have been performed to measure the antiviral activity of Sinupret(®) oral drops (hereinafter referred to as "oral drops") and Sinupret(®) dry extract (hereinafter referred to as "dry extract"), in vitro against a broad panel of both enveloped and non-enveloped human pathogenic RNA and DNA viruses known to cause infections of the upper respiratory tract: influenza A, Chile 1/83 (H1N1) virus (FluA), Porcine Influenza A/California/07/2009 (H1N1) virus (pFluA), parainfluenza type 3 virus (Para 3), respiratory syncytial virus, strain Long (RSV), human rhinovirus B subtype 14 (HRV 14), coxsackievirus subtype A9 (CA9), and adenovirus C subtype 5 (Adeno 5). Concentration-dependent antiviral activity (EC(50) between 13.8 and 124.8 µg/ml) of Sinupret(®) was observed against RNA as well as DNA viruses independent of a viral envelope. Remarkable antiviral activity was shown against Adeno 5, HRV 14 and RSV in which dry extract was significantly superior to oral drops. This could be ascertained with different assays as plaque-reduction assays in plaque forming units (PFU), the analyses of a cytopathogenic effect (CPE) and with enzyme immunoassays (ELISA) to determine the amount of newly synthesised virus. Our results demonstrate that Sinupret(®) shows a broad spectrum of antiviral activity in vitro against viruses commonly known to cause respiratory infections.

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