Human interferon-inducible protein 10 (IP-10) differs from most chemokines in its apparent specificity for activated T lymphocytes. We hypothesized that IP-10 was relevant not only for recruiting T cells to inflammatory sites, but also for regulating cytokine synthesis patterns. We examined the effect of recombinant human IP-10 (rhIP-10) on human interferon gamma (IFN-gamma) and interleukin 4 (IL-4) production by fresh peripheral blood mononuclear cells. We demonstrate for the first time that this CXC chemokine selectively up-regulates human T cell cytokine synthesis, with enhancement selectively targeted to promotion of Th1-like dominance. Superantigen (TSST-1), soluble anti-CD3 mAb, and phytohemagglutinin were used to activate distinct intracellular signaling pathways, thereby inducing quantitatively different IFN-gamma:IL-4 ratios. Selective enhancement of IFN-gamma responses was consistently observed, with median increases of 105-470%. Environmental antigens (Ag) were used to evaluate IP-10's effect on CD4-dependent, chloroquine-sensitive cytokine synthesis. Ag-driven IFN-gamma responses exhibited median 19- to 30-fold increases in the presence of nanomolar concentrations of rhIP-10. IL-4 responses were neither enhanced nor inhibited under any of the conditions tested. These findings suggest a potential role for this T cell-focused chemokine in maintenance of the default Th1-like responses usually seen to environmental Ag and indicate a potential application in the modulation of Ag-driven responses in vivo.

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RationaleIn party circuits dexamphetamine is frequently used in combination with alcohol. It is hypothesized that co-administration of dexamphetamine to alcohol might reduce the sedative effects of alcohol, but may potentiate risk-taking behaviour.ObjectivesThe study was aimed at assessing the effects of alcohol, dexamphetamine and the combination of both on simulated driving and cognitive performance.MethodEighteen subjects participated in a randomized, crossover, placebo-controlled study employing four conditions: 10 mg dexamphetamine, 0.8 g/kg alcohol, 10 mg dexamphetamine + 0.8 g/kg alcohol, and placebo. Fundamental driving skills and risk-taking behaviour were assessed in a driving simulator. Subjects also completed vigilance and divided attention tasks, and subjective ratings.ResultsMean BAC levels during simulated driving were between 0.91‰ and 0.64‰. Subjects using alcohol showed a significantly larger mean standard deviation of lateral position and shorter accepted gap time and distance. Use of alcohol or dexamphetamine + alcohol was associated with a higher frequency of red light running and collisions than the dexamphetamine or placebo conditions. Performance of vigilance and divided attention tasks was significantly impaired in the alcohol condition and, to a lesser degree, in the dexamphetamine + alcohol condition.ConclusionSingle doses of 0.8 g/kg alcohol increased risk-taking behaviours and impaired tracking, attention and reaction time during a 3-h period after drinking when BACs declined from 0.9 to 0.2 mg/ml. The stimulatory effects of co-administration of dexamphetamine 10 mg were not sufficient to overcome the impairing effects of alcohol on skills related to driving.

The mechanism of air travel-related venous thrombosis is unclear. Although immobility plays a pivotal role, other factors such as fluid loss may contribute. We investigated whether fluid loss occurred more in individuals with coagulation activation after air travel than in subjects without. As a secondary aim, we investigated whether fluid loss per se occurred during air travel. In this crossover study, 71 healthy volunteers were exposed to eight hours of air travel, eight hours immobilization in a cinema, and a daily-life control situation. Markers of fluid loss (haematocrit, serum osmolality and albumin) and of coagulation activation were measured before and after each exposure. The study included 11 volunteers with and 55 volunteers without coagulation activation during the flight. The change in parameters of fluid loss was not different in volunteers with an activated clotting system from those without (difference between groups in haematocrit: -0.6%, 95% confidence interval [CI]: -1.9 to 0.6). On a group level, mean haematocrit values decreased during all three exposures. However, in some individuals it increased, which occurred in more participants during the flight (34%; 95% CI 22 to 46) than during the daily-life situation (19%; 95% CI 10 to 28). These findings do not support the hypothesis that fluid loss contributes to thrombus formation during air travel.