http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9439 Background Airway hyperresponsiveness (AHR) in asthmatics includes a variable component that persists following an allergen challenge. This may be dissociated from inflammatory cell recruitment, implying a role for resident pulmonary cells in regulating the response. Objective Using improved methods of assessing AHR in a mouse model of allergic airway disease, to investigate the basis of the development of prolonged AHR. Method BALB/c mice were systemically sensitized and then challenged with aerosolized ovalbumin (OVA). Airway and tissue responsiveness were measured at baseline and at 1 day, and 1, 2 and 3 weeks after the last OVA challenge. Inflammatory cell numbers in BALF and levels of mRNA for eotaxin-1 and -2, IFN-γ , IL-5 and -13 in the lung were measured at each time-point. In further experiments, the roles of IFN-γ and of CCR3⁺ and CD4⁺ cells in the development of prolonged AHR were assessed by blockade or depletion with monoclonal antibodies. The role of pulmonary macrophages was assessed by selective chemical depletion of these cells. Results Airway responsiveness was increased above baseline at 1 day after the last OVA challenge, and this was sustained for 1 week. In contrast, tissue-specific responsiveness was only significantly increased above baseline at 1 day. Development of prolonged AHR was inhibited by neutralization of IFN-γ or by depletion of pulmonary macrophages, but not by depletion of either CD4⁺ T cells or CCR3⁺ eosinophils. Conclusion An interaction between IFN-γ and pulmonary macrophages contributed to the prolongation of airway hyperresponsiveness. In contrast, T cells and eosinophils did not contribute to prolongation of AHR. These findings emphasize the importance of the innate host response in the development of manifestations of asthma, as well as its potential relevance as a target for therapeutic intervention. 2011-11-21T05:00:03.783Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1055 Atherosclerosis is an inflammatory response, probably to a range of initiating causes. Chronic infection with Chlamydia pneumoniae (C.pn) has been suggested as one cause, but the nature of the association is controversial, in large part due to lack of an identified mechanism to link infection with the atherosclerotic process in man. This study examined 139 consecutive subjects with stable chest pain, with the aim of correlating the serological status of C.pn infection with the pattern of secretion of cytokines from CD4⁺ T lymphocytes. C.pn seropositive subjects secreted significantly more interleukin (IL)-4 than did those who were C.pn seronegative (P = 0·02). No significant difference was noted for secreted interferon (IFN)-γ. The amount of secreted IL-4, but not of secreted IFN-γ, correlated positively with the extent of coronary artery disease (P = 0·006). A similar correlation with secreted IL-4 was not identified with Helicobacter pylori infection. These results support the hypothesis that C.pn infection contributes to the inflammatory process responsible for coronary artery atherosclerosis. The method used to detect cytokine secretion involves ligation of CD40L on blood CD4⁺ T cells, which may have relevance to tissue events. 2010-04-27T06:07:54.271Z ]]>