By RT-qPCR, mRNA of IL-8 showed an immediate down-regulation followed by a slow up-regulation which was statistically significant (P = 0.02) in a regression model against time ( Fig. 1). There was no discernible effect of vaccination on IL-1β ( Fig. 2) or IFNγ ( Fig. 3). TNFα expression was undetectable in a considerable number of samples: in 6 cases there was no detectable expression before or after vaccination; in 5 cases mRNA was detected only before vaccination, and in 5 cases only after vaccination. In the remaining 5 cases, www.selleckchem.com/B-Raf.html there

was a modest down-regulation, but this was not statistically significant in view of the small number of data pairs. HIV-infected participants did not differ from HIV-uninfected www.selleckchem.com/products/3-deazaneplanocin-a-dznep.html participants with

respect to changes in cytokine expression following vaccination, and those biopsies in which TNFα expression was not detectable were not more likely to come from HIV-infected participants (data not shown). The safety of live, attenuated vaccines in HIV infected people is of paramount importance if vaccines are to play any role in reducing the burden of common diseases in tropical populations. In this study we found that in 34 HIV seropositive adults given a total of 58 courses of three live, attenuated oral vaccines there was no evidence of serious adverse events: no hospitalisations, no episodes of diarrhoea requiring treatment, no significant febrile illnesses, and no increase in symptoms such as abdominal pain, nausea or loss of appetite. There was no evidence of haematological toxicity. If we accept that oral vaccines do not next cause diarrhoea after 7 days have elapsed beyond the final dose of vaccine, there was no increase in diarrhoea. The interpretation of diarrhoea data in this setting is difficult if we use HIV seronegative adults as the comparison group, as at any given point

in time HIV infected adults have a higher incidence rate of diarrhoeal disease [19]. We believe that this explains the higher diarrhoea incidence after 7 days following vaccination. Our data are compatible with the hypothesis that these vaccines lead to a modest increase in mild, transient episodes of diarrhoea beyond 1 week in HIV infected adults. They are also explicable with there being a consistently increased risk of diarrhoea in HIV throughout the period of observation. We found no evidence that vaccines induce intestinal inflammation. IL-8 is a chemokine expressed by epithelial cells on contact with potentially invasive bacteria. The other, pro-inflammatory, cytokines showed no change in expression over the week following vaccination. While these data do not rule out a pathogenic effect of these vaccines, they offer considerable reassurance that rotavirus vaccine does not induce inflammation.

Dr Devin holds board membership with Alcon, Allergan, Bayer, and Novartis; consults with Alcon, Allergan, Bayer, Novartis, Ophthotech, and Thea; receives payment for lectures, including service on speakers’ bureaus, from Alcon, Allergan, Bayer, and Novartis; and receives payment for development of educational presentations from Alcon, Allergan, Bayer, and Novartis. Dr Mauget-Faÿsse receives consulting fees or honoraria, with fees going to the institution, from Molecular

Partners and support for travel to meetings Temozolomide mouse for the study of other purposes from Molecular Partners. Relevant financial activities outside the submitted work include board membership in Bayer and Novartis; payment for lectures, including service on speakers’ bureaus, with fees going to the institution; from Bayer, Heidelberg, Novartis, and Thea; travel/accommodation/meeting expenses unrelated to activities listed, with fees going to the institution from Bayer, Heidelberg, Novartis, and Thea. Dr Kolář receives consulting honoraria

from Molecular Partners. Relevant financial activities outside the submitted work include consultancy with Alcon, Bayer, and Novartis and payment for lectures, including service on speakers’ bureaus, from Alcon, Bayer and Novartis. Dr Wolf-Schnurrbusch work under consideration for publication: payment for gradings to institution. Dr Framme holds board membership with Allergan, Bayer and Novartis, is a consultant for Bayer, and receives payment for lectures, including service on speakers’ bureaus, from Bayer, Heidelberg and Novartis. Dr Gaucher

holds board membership in Allergan, Bayer and Novartis learn more and receives payment for development of educational presentations, with fees going to the institution, from Novartis; and receives travel/accommodation/meeting expenses unrelated to activities listed from Alcon, Bausch & Lomb, Bayer, and Novartis. Dr Querques receives consulting fees or honoraria from Molecular Partners; holds board membership in Alimera, Allergan and Bayer; and is a consultant to Alcon, Alimera, Allergan, Bayer, Bausch & Lomb, Molecular Partners, Novartis, and Ophthotech. Dr Stumpp holds employment, patents and stock/stock options in Molecular Partners. Dr Wolf has Rolziracetam received a grant, with fee to the institution, from Molecular Partners; consulting fees or honoraria, with fees to the institution, from Molecular Partners; support for travel to meetings for the study of other purposes from Molecular Partners; is a board member of EURETINA; receives consultancy fees that go to the institution from Allergan, Bayer, Heidelberg Engineering, Novartis, and Optos; and receives fees for expert testimony, with fees going to the institution, from Bayer. Molecular Partners AG, Zurich, Switzerland, provided support for the study and participated in study design; conducted the study; and provided data collection, management and interpretation. The study is registered at ClinicalTrials.gov under the identifier: NCT01086761.