IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx?

BACKGROUND: The role of Th2 cells (producing interleukin (IL-)4, IL-5 and IL-13) in allergic asthma is well-defined. A distinct proinflammatory T cell lineage has recently been identified, called Th(17 )cells, producing IL-17A, a cytokine that induces CXCL8 (IL-8) and recruits neutrophils. Neutrophilic infiltration in the airways is prominent in severe asthma exacerbations and may contribute to airway gland hypersecretion, bronchial hyper-reactivity and airway wall remodelling in asthma. AIM: to study the production of IL-17 in asthmatic airways at the mRNA level, and to correlate this with IL-8 mRNA, neutrophilic inflammation and asthma severity. METHODS: We obtained airway cells by sputum induction from healthy individuals (n = 15) and from asthmatic patients (n = 39). Neutrophils were counted on cytospins and IL-17A and IL-8 mRNA expression was quantified by real-time RT-PCR (n = 11 controls and 33 asthmatics). RESULTS: Sputum IL-17A and IL-8 mRNA levels are significantly elevated in asthma patients compared to healthy controls. IL-17 mRNA levels are significantly correlated with CD3γ mRNA levels in asthmatic patients and mRNA levels of IL-17A and IL-8 correlated with each other and with sputum neutrophil counts. High sputum IL-8 and IL-17A mRNA levels were also found in moderate-to-severe (persistent) asthmatics on inhaled steroid treatment. CONCLUSION: The data suggest that Th(17 )cell infiltration in asthmatic airways links T cell activity with neutrophilic inflammation in asthma

Pentraxin 3 (PTX3) Expression in Allergic Asthmatic Airways: Role in Airway Smooth Muscle Migration and Chemokine Production

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. PTX3 is produced by immune and structural cells. However, very little is known about the expression of PTX3 and its role in allergic asthma.We sought to determine the PTX3 expression in asthmatic airways and its function in human airway smooth muscle cells (HASMC). In vivo PTX3 expression in bronchial biopsies of mild, moderate and severe asthmatics was analyzed by immunohistochemistry. PTX3 mRNA and protein were measured by real-time RT-PCR and ELISA, respectively. Proliferation and migration were examined using (3)H-thymidine incorporation, cell count and Boyden chamber assays.PTX3 immunoreactivity was increased in bronchial tissues of allergic asthmatics compared to healthy controls, and mainly localized in the smooth muscle bundle. PTX3 protein was expressed constitutively by HASMC and was significantly up-regulated by TNF, and IL-1β but not by Th2 (IL-4, IL-9, IL-13), Th1 (IFN-γ), or Th-17 (IL-17) cytokines. In vitro, HASMC released significantly higher levels of PTX3 at the baseline and upon TNF stimulation compared to airway epithelial cells (EC). Moreover, PTX3 induced CCL11/eotaxin-1 release whilst inhibited the fibroblast growth factor-2 (FGF-2)-driven HASMC chemotactic activity.Our data provide the first evidence that PTX3 expression is increased in asthmatic airways. HASMC can both produce and respond to PTX3. PTX3 is a potent inhibitor of HASMC migration induced by FGF-2 and can upregulate CCL11/eotaxin-1 release. These results raise the possibility that PTX3 may play a dual role in allergic asthma

The feasibility of a physical activity counselling program in children with congenital heart disease

Background: Children with congenital heart disease (CHD) now have excellent survival into adulthood but have an increased risk of cardiovascular disease. One important strategy to mitigate this risk is through physical activity (PA) promotion. It is currently not known how to optimally improve PA in children with CHD. We aimed to determine the feasibility and acceptability of a theoretically based virtual PA counselling intervention for children and families with CHD and explore PA changes after the intervention. Methods: We designed a 12-week family-centered, individualized, virtual PA counselling intervention based on behaviour change theory. Children ages 9 to 12 with moderate-to-complex CHD were recruited from BC Children’s Hospital. At baseline, we measured participants’ moderate-to-vigorous PA using accelerometers and readiness to change their PA using a questionnaire to determine intervention eligibility. Participants who were not meeting the PA guidelines and expressed readiness to change qualified for the PA counselling intervention. The intervention consisted of 6 sessions with a PA counsellor via Zoom where participants learned strategies to promote PA through workbook activities. We measured PA again at the intervention midpoint, post-intervention, and one year follow-up. Intervention feasibility (recruitment, retention, completion of PA measures, remote delivery, session length, and time commitment) and acceptability (intervention compliance and participant feedback via interviews and surveys) were assessed. Results: Despite lower than anticipated recruitment rates, this intervention was feasible based on high retention, completion of PA measures, and remote delivery success. Participants were committed and engaged with the intervention as seen by excellent attendance and activity completion rates, and positive participant feedback via qualitative and quantitative measures. There were no significant differences in objective or subjective PA measures from pre-intervention to post-intervention but there were likely intervention responders and non-responders, and more data is needed to determine intervention sustainability. Conclusion: This PA counselling intervention is feasible and acceptable to families and children with CHD. All measures of acceptability encourage that the intervention is engaging and well received by children with CHD. Preliminary objective PA data suggests that the intervention may have facilitated increased PA for some participants.Medicine, Faculty ofMedicine, Department ofGraduat