In chronic inflammatory diseases like asthma or rheumatoid arthritis, erroneous and exaggerated accumulation of leukocytes in a tissue inadvertently causes the body harm. Several efficient anti-inflammatory drugs exist, for example corticosteroids and cyclo-oxygenase inhibitors. However, these drugs have potent and diverse effects and often act by inhibiting events subsequent to initiation of the inflammatory response, leading to more or less severe side-effects, especially when used in high doses for long periods of time. For this reason, strategies aimed at early inhibition of recruitment and activation of leukocytes have been suggested as safer and more specific approaches to reduce inflammation. Leukocyte adhesion to activated endothelium is a prerequisite to the following activation and extravasation, and takes place in the initial phase of inflammation. By using a model that allows leukocytes to adhere to tumour necrosis factor (TNF)-activated endothelial cells, thus mimicking aspects of an inflammatory reaction, we found that uridine, 4-thiouridine and isomaltitol could all reduce adhesion. This suggested that they may have anti-inflammatory potential. We therefore tried the three substances in a Sephadex-induced lung inflammation model and found that uridine and 4-thiouridine have several anti-inflammatory effects, such as being able to reduce leukocyte accumulation, decrease TNF protein levels and partly inhibit the oedema induced by Sephadex. Isomaltitol turned out to have immunomodulating, rather than anti-inflammatory, effects, which could be of interest in diseases where inadequate inflammatory responses are a problem.

Une antisepsie-désinfection (ATS-D) efficace est fondamentale si l'on considère le manque de traitements antiviraux spécifiques, l'émergence de nouveaux virus et l'accroissement du nombre d'infections nosocomiales virales. A ce jour, une seule norme Européenne, la norme NF EN 14476+A1, propose un cadre pour évaluer l'activité ATS-D antivirale en médecine Humaine et certaines améliorations sont encore nécessaires.Dans ce but, nous avons développé et validé, biologiquement et physico-chimiquement, un protocole pour évaluer l'activité ATS-D antivirale. Ce dernier est basé sur une méthode originale de filtration sur gel faisant appel à des colonnes de Séphadex™ G-25 et G-10 de notre conception comme moyen de neutralisation. Nous avons ainsi évalué, sur le coronavirus Humain 229E (HCoV 229E), les activités ATS-D de deux molécules de référence, la chlorhexidine (CHX) et l'hexamidine (HXM), ainsi que de deux calixarènes : le tetra-para-sulfonato-calix[4]arène (C[4]S) et le 1,3-bis(bithiazolyl)-tetra-para-sulfonato-calix[4]arène (C[4]S-BTZ). Selon la norme Européenne, pour qu'une formulation puisse prétendre à une activité ATS-D antivirale, il faut qu'elle induise une diminution de 4 log10 dans les titres viraux. L'HXM et le C[4]S n'ont montré qu'une très faible activité vis à vis du HCoV 229E. La CHX a montré quant à elle une activité beaucoup plus intéressante bien qu'elle ne puisse néanmoins pas prétendre à une activité ATS sur le HCoV 229E. Enfin, le C[4]S-BTZ a montré une activité comparable, voire meilleure, que la CHX. Son activité s'est en effet avérée plus rapide, rémanente et dénuée de cytotoxicité, contrairement à la CHX / Efficient antisepsis-disinfection is fundamental, considering the lack in antiviral treatments, the emergence of new viruses and the raising of viral nosocomial infections. Only one European Standard (NF EN 14476 + A1) proposes a frame to evaluate antiseptic antiviral activity in Human medicine and some improvements are still needed. We thus developed and validated, biologically and physico-chemically, a virucidal assay based on an original gel filtration method, using “in-house” G-25 and G-10 Sephadex™ columns, as neutralization method. We evaluated, on the Human coronavirus 229E (HCoV 229E), the antiseptic activity of two reference molecules, chlorhexidine (CHX) and hexamidine (HXM), and of two new potent antiviral drugs: the tetra-para-sulfonatocalix[4]arene (C[4]S) and the 1,3-bis(bithiazolyl)-tetra-para-sulfonato calix[4]arene (C[4]S-BTZ). A 4 log10 reduction in viral titers is required, according to the European Standard.HXM and C[4]S showed almost no activity on the HCoV 229E. Considering the CHX, it showed a quite interesting activity, even if it did not reach the threshold to pretend to an antiseptic activity on the HCoV 229E. Finally, The C[4]S-BTZ showed a comparable activity to the CHX, and even better. Thanks to this original method, we could highlight a new interesting molecule, the C[4]S-BTZ, which showed a close activity to the CHX, but faster, residual and exempt of cytotoxicity, whereas chlorhexidine did