Changes in immune regulation in response to examination stress in atopic and healthy individuals

BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.     

Modulation of cytokine production from an EpiOcular corneal cell culture model in response to Staphylococcus aureus superantigen

The present study investigated the hypothesis that Staphylococcus aureus enterotoxin B (SEE) produces epithelial cell death and releases inflammatory cytokines that produce stromal infiltration during contact lens induced peripheral ulceration. Epithelial cells were incubated with different doses of SEB for various time periods. Culture supernatants were assayed for cytokines IL- lo, IL-6 and chemotactic agents IL-8 and LTB,. SEE induced the production of IL- I p and IL-8. Epithelial cells exposed for longer periods (48 h) with low concentrations of SEB produced significantly higher levels (N0.02) of IL-Ip and IL-8 (P<0.05) compared t o a 24 h exposure. SEB did not induce the production o f IL-6 and     

Overexpression of suppressor of cytokine signalling-5 augments eosinophilic airway inflammation in mice

BACKGROUND: Enhanced expression of the suppressor of cytokine signalling (SOCS)-5 might be of therapeutic benefit for T-helper type 2 (Th2) dominant diseases, as its expression is reported to result in a reduction of Th2 differentiation in vitro due to the inhibition of IL-4 signalling. OBJECTIVE: To investigate the regulatory role of SOCS-5 in vivo, we explored the phenotype of an experimental asthma model developed in SOCS-5 transgenic (Tg) mice. METHODS: The SOCS-5 Tg mice or wild-type (WT) mice were sensitized and repeatedly challenged with ovalbumin (OVA). We examined bronchoalveolar lavage fluid (BALF), lung specimens, and airway hyperresponsiveness (AHR) to methacholine. RESULTS: The production of IFN-gamma by CD4(+) T cells from unprimed SOCS-5 Tg mice was significantly increased in comparison with unprimed wild-type mice, indicating that SOCS-5 Tg mice have a Th1-polarizing condition under natural conditions. However, in an asthma model, significantly more eosinophils in the airways and higher levels of IL-5 and IL-13 in BALF were observed in the SOCS-5 Tg than the wild-type mice. AHR in the asthma model of SOCS-5 Tg was also more enhanced than that of wild-type mice. OVA-stimulated CD4(+) T cells from the primed SOCS-5 Tg mice produced significantly more IL-5 and IL-13 than CD4(+) T cells from wild-type mice. CONCLUSION: Our results demonstrate that the overexpression of SOCS-5 does not inhibit Th2 response, but rather augments the phenotype of the asthma model in vivo. This finding throws into question the therapeutic utility of using enhancement of SOCS-5 expression for Th2-dominant disease.     

The Hemodynamic Mechanisms of Lung Injury and Systemic Inflammatory Response Following Brain Death in the Transplant Donor

Brain-dead donors are the major source of lungs for transplantation. Brain death is characterized by two hemodynamic phases. Initially, massive sympathetic discharge results in a hypertensive crisis. This is followed by neurogenic hypotension. Up-regulation of pro-inflammatory mediators occurs in all organs and lung injury develops; this can adversely affect graft function post-transplantation. The mechanisms of the systemic and lung inflammation are unknown. We hypothesized that the hemodynamic changes are responsible for these inflammatory phenomena. Brain death was induced by intra-cranial balloon inflation in rats. This resulted in hypertensive crisis, followed by hypotension. There was a significant increase in blood neutrophil CD11b/CD18 expression and pro-inflammatory cytokine levels in serum and bronchoalveolar lavage, compared with control animals. Rupture of the capillary-alveolar membrane was demonstrated by electron microscopy. Elimination of the hypertensive response by α-adrenergic antagonist pre-treatment prevented inflammatory lung injury, reduced the systemic inflammatory markers and preserved capillary-alveolar membrane integrity. Correction of the neurogenic hypotension with noradrenaline ameliorated the systemic inflammatory response and improved oxygenation. We conclude that the sympathetic discharge triggers systemic and lung inflammation, which can be further enhanced by neurogenic hypotension. Management of the brain-dead donor with early anti-inflammatory treatment and vasoconstrictors is warranted.     

单核吞噬细胞应答伤寒沙门菌的实验研究

目的 研究单核吞噬细胞应答伤寒沙门菌的机理。方法 采用体外培养的PMA分化的THP－1细胞，检测其内化和杀伤胞内伤寒沙门菌的活性，以及伤寒沙门菌诱导PMA分化的THP－1细胞产生TNF－α和IL－12的情况。结果 PMA分化的THP－1细胞内化和杀伤Vi阴性伤寒沙门菌的活性明显高于内化和杀伤Vi阳性伤寒沙门菌的活性。IFN－γ明显中此活性。伤寒沙门菌诱导PMA分化的THP－1细胞可以产生一定量的TNF－α和IL－12，然而，IFN－γ活化的PMA分化的HTP－1细胞产生TNF－α和IL－12的量明显增加。结论 伤寒沙门菌在单核吞噬细胞中的存活可能与Vi抗原的存在有关；IFN－γ在调节机体细胞免疫，防循伤寒沙门菌感染中起着重要的作用。     

The influence of anaesthetic techniques and type of delivery on peripartum serum interleukin-6 concentrations

Background: Interleukin-6 is a pleiotropic cytokine with a wide range of physiological activities. It plays an important role in the immuno-neuro-humoral axis during stress and surgery.
Methods: Serum interleukin-6 in parturients was measured on hospital admission, immediately after birth and 12 and 24 hours later. All parturients had uncomplicated pregnancies, and delivered vaginally without (n=31) or with (n=20) epidural analgesia, or underwent Caesarean section under epidural (n=20) or general (n=10) anaesthesia.
Results: Serum interleukin-6 assayed immediately following Caesarean section was low, but peaked 12 hours later, irrespective of the anaesthetic technique or other foetomaternal characteristics. Patients who delivered vaginally showed the highest interleukin-6 levels immediately after delivery. These were positively correlated with serum interleukin-6 on admission and duration of labour. Serum interleukin-6 was significantly higher in parturients who had epidural analgesia, and was significantly lower in those receiving intravaginal prostaglandins compared to those without prostaglandins.
Conclusion: The interleukin-6 response after Caesarean section can be explained by a generalized acute phase response to surgery, with no anaesthetic, maternal or neonatal interference. The rapid increase in peripartum serum interleukin-6 levels after vaginal delivery reflects, in part, cervical ripening or labour, their physiological triggers and psychological or physical stress. Regional anaesthesia, duration of labour and exogenous prostaglandin administration can modulate the peripartum interleukin-6 response and subsequently the physiological effects of this cytokine.