Properdin deficiency protects from 5-fluorouracil-induced small intestinal mucositis in a complement activation-independent, interleukin-10-dependent mechanism

Intestinal mucositis is a serious complication of chemotherapy that leads to significant morbidity that may require dose or drug adjustments. Specific mitigating strategies for mucositis are unavailable, due partly to an incomplete understanding of the pathogenic mechanisms. We have previously shown an effect of properdin, a positive regulator of complement activation, in models of colitis. Here we use properdin-deficient (P) mice to interrogate the role of properdin and complement in small intestinal mucositis. Mucositis was induced by five daily injections of 5-fluorouracil (5-FU) in wild-type (WT), P, interleukin (IL)-10and properdin/IL-10double knock-out (DKO) mice. At the time of euthanasia their jejunum was collected for histology, immunohistochemistry and cytokine and complement activation measurements. Complement became activated in mice receiving 5-FU, indicated by increased intestinal levels of C3a and C5a. Compared to WT, Pmice experienced significantly less mucositis, despite C3a levels as high as inflamed WT mice and slightly less C5a. Conversely, Pmice had higher intestinal levels of IL-10. IL-10 expression was mainly by epithelial cells in both uninflamed and inflamed Pmice. IL-10mice proved to be highly susceptible to mucositis and DKO mice were equally susceptible, demonstrating that a lack of properdin does not protect mice lacking IL-10. We interpret our findings to indicate that, to a significant extent, the inflammation of mucositis is properdin-dependent but complement activation-independent. Additionally, the benefit achieved in the absence of properdin is associated with increased IL-10 levels, and IL-10 is important in limiting mucositis

An occupational justice perspective on playing football and living with mental distress

© 2020 The Author(s). Physical inactivity is a global public health priority, yet people living with a disability or long-term health condition, such as those who experience mental distress, continue to face inequalities and barriers to participation in sport and physical activity. These inequalities are considered an occupational injustice, in terms of participation in health enhancing occupations being restricted for these groups of people, despite them wanting to be more active. This study aimed to gain an in-depth understanding of the nature and value of participating in a UK based community football project, for people with experience of mental distress. Twenty-three people took part in this first strand of a larger participatory action research study, which used the World Café as a method for structuring and recording conversations. Data from the three World Café events were analysed collectively and thematically. The study’s findings reveal tensions, nuances, and subtleties that exist in relation to the reciprocal relationship between playing football and people’s health and well-being. The complexity of enabling participation in sport and physical activity amongst marginalised groups, such as people with experience of mental distress, is highlighted.Elizabeth Casson Trus

The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL-4 and IL-10

BACKGROUND AND PURPOS