Temperature has been known to be an important factor for in vitro studies where human cell cultures are infected with HRV (human Rhinovirus). The mechanisms behind the temperature effect on the struggle between virulence and cellular defense, are still largely unknown and may be a crucial part in finding a treatment to the common cold. In this study we focused on a few cellular key elements in this struggle and observed behavior changes in regards to the pre-infection growth temperature and the temperature during the viral infection. Past studies have focused mainly on the temperature post inoculation, but here we also wanted to correlate virulence to the growth temperatures preceding the viral infection. We found that the growth temperature of the cell did indeed affect its response to the HRV. If the cells had been growing in an optimal body temperature of 37°C before getting virally infected at 33°C, the viability of the cells did decrease in comparison to cells that had been growing in 33°C from before the viral infection. We could also observe a significant temperature dependence regarding IL-8 release upon HRV inoculation. HRV strive to block induction of inflammatory cytokines such as interferons and IL-1. It may be that impaired IL-8 release at lower temperatures will prevent important danger signals alerting the immune system when cytokine signaling is otherwise hampered by viral intervention.

Yes / We report an evaluation of the cytotoxicity of a series of electron-deficient (16-electron) half-sandwich precious metal complexes of ruthenium, osmium and iridium ([Os/Ru(η6-pcymene)( 1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (1/2), [Ir(η5-pentamethylcyclopentadiene)(1,2-dicarba-closo-dodecarborane- 1,2-dithiolato)] (3), [Os/Ru(η6-p-cymene)(benzene-1, 2-dithiolato)] (4/5) and [Ir(η5-pentamethylcyclopentadiene) (benzene-1,2-dithiolato)] (6)) towards RAW 264.7 murine macrophages and MRC-5 fibroblast cells. Complexes 3 and 6 were found to be non-cytotoxic. The anti-inflammatory activity of 1–6 was evaluated in both cell lines after nitric oxide (NO) production and inflammation response induced by bacterial endotoxin lipopolysaccharide (LPS) as the stimulus. All metal complexes were shown to exhibit dose-dependent inhibitory effects on LPS-induced NO production on both cell lines. Remarkably, the two iridium complexes 3 and 6 trigger a full anti-inflammatory response against LPS-induced NO production, which opens up new avenues for the development of non-cytotoxic anti-inflammatory drug candidates with distinct structures and solution chemistry from that of organic drugs, and as such with potential novel mechanisms of action. / We thank the Royal Society (University Research Fellowship No. UF150295 to NPEB), and the University of Bradford for financial support.

Nickel is a widely used metal in industrial and commercial applications, being both workable and highly resistant to corrosion. Certain nickel compounds are known human carcinogens, but not all nickel compounds are equally hazardous. A robust method of assessing the carcinogenic potential of various nickel compounds is needed in order to determine safe occupational exposure levels. This work attempts to develop an in vitro mammalian cell culture method for assessing the carcinogenic and toxic potential of nickel compounds by metabolic and cell cycle analysis. Two cell lines, C3H/10T1/2 and MRC-5, were used. Measurements of extracellular metabolites by enzymatic methods and HPLC were combined with cell counts and cell cycle and apoptosis analysis by flow cytometry. This work shows that nickel sulphate can elicit a metabolic response similar to that of organic carcinogens, though the underlying mechanisms are likely different. / Vale Canada Limited, NSERC

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