Impact of transfusion of apoptotic and necrotic thymocytes on the survival of mice with sepsis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of transfusion of apoptotic and necrotic thymocytes prior to sepsis on the survival rate of mice.</p><p><b>METHODS</b>BALB/c mice are divided into 3 groups and received intravenous injection of PBS (control), apoptotic thymocytes, or necrotic thymocytes. Three days later, cecal ligation and puncture (CLP) were performed to induce sepsis in these mice, and their survival and organ damage were observed.</p><p><b>RESULTS</b>The survival rates of mice in PBS group was 44.6% at the end of first week after CLP, and obvious lung and kidney damages were observed. A significant increase in the survival rate was found in apoptotic cell transfusion group (69.6%, P=0.012), with also lessened lung and kidney damages. The survival rate of mice in necrotic cell transfusion group was only 31.6% at 2 weeks, significantly lower than that in PBS group (P=0.035), and the lung and kidney damage was even more obvious.</p><p><b>CONCLUSION</b>Transfusion of apoptotic thymocytes 3 days before induction of sepsis can reduce organ damage and improve the survival rate of mice, while necrotic cell transfusion produces the opposite effect.</p>

Effect of FK506 on cytokine secretion in whole blood / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of FK506 on cytokine secretions in whole blood from healthy individuals.</p><p><b>METHODS</b>Blood samples collected from healthy volunteers were co-cultured with different concentrations of FK506 and stimulated with PMA and IONO. The concentrations of 8 cytokines including IL-2, IL-6, IL-12, IL-17, IFN-gamma, TNF-alpha, GM-CSF and G-CSF were detected by Bio-Plex suspension system.</p><p><b>RESULTS</b>Compared with the control group, high-concentration FK506 (20 ng/ml) significantly inhibited the secretions of IL-2, IL-6, IL-12, IL-17, IFN-gamma, TNF-alpha, GM-CSF and G-CSF. At a moderate concentration (5 ng/ml), FK506 inhibited the secretion of GM-CSF significantly.</p><p><b>CONCLUSION</b>FK506 effectively inhibits the secretion of proinflammatory cytokines including IL-6, IFN-gamma and TNF-alpha and also the secretion of IL-2, IL-12, IL-17, GM-CSF and G-CSF. FK506 might play the role of immunosuppression by inhibiting the production of these cytokines by the immune cells. Monitoring the levels of these cytokines might be a potential method for evaluating the adequacy of FK506 doses administered.</p>

Differences in the response to sepsis between C57BL/6 and BALB/c mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the responses to sepsis between C57BL/6 and BALB/c mice.</p><p><b>METHODS</b>Thirty C57BL/6 mice and 30 BALB/c mice were randomized into sham-operated group and sepsis group (n=15). Sepsis model was established by cecal ligation puncture (CLP) in the mice, and 6 h after the operation, 5 mice from each group were selected randomly for cytokine detection including IL-1beta, IL-2, IL-4, IL-5, IL-10, GM-CSF, IFN-gamma and TNF-alpha by Bio-plex. The other 10 mice in each group were used for survival analysis.</p><p><b>RESULTS</b>The survival rates of BALB/c and C57BL/6 mice were both 100% in one week after the sham operation, but lowered to 10% and 50% in one week after CLP, respectively. The survival rate of C57BL/6 mice was significantly lower than that of BALB/c mice (P<0.05). After CLP, C57BL/6 mice showed significantly greater IL-4, TNF-alpha and IL-10 production than the sham-operated mice, but the concentrations of the 8 cytokines in BALB/c mice after CLP showed no significant increment.</p><p><b>CONCLUSION</b>Compared with BALB/c mice, C57BL/6 strain mouse is more sensitive to sepsis.</p>

Effects of apoptotic lymphocytes on proinflammatory cytokine secretion by hepatic sinusoidal endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of apoptotic lymphocytes on the secretion of cytokines by hepatic sinusoidal endothelial cells (HSEC).</p><p><b>METHODS</b>Human HSEC cells were co-cultured for 16 h with allogenetic apoptotic lymphocytes induced by UVB irradiation. The supernatants were collected and the levels of interleukin-2, interferon-gamma, and tumor necrosis factor-alpha were detected by Luminex technique.</p><p><b>RESULTS</b>All the cytokines were down-regulated by about 50% in HSECs after co-culture with the apoptotic lymphocytes as compared with those in the control group (P<0.05).</p><p><b>CONCLUSIONS</b>Co-culture with apoptotic lymphocytes can down-regulate the secretion of pro-inflammatory cytokines in HSECs, which may contribute to tolerogenic microenvironment in the liver.</p>

Necrotic cells induce and promote inflammatory responses in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of necrotic cells on the secretion of inflammatory cytokines.</p><p><b>METHODS</b>RAW264.7 macrophages and necrotic mouse thymocytes induced by heating were incubated for 18 h at a ratio of 5:1 in the absence or presence of lipopolysaccharide (LPS, 100 ng/ml). The supernatant of the cell culture was collected and the expression and secretion of the pro-inflammatory cytokines were measured using Bio-Plex suspension system.</p><p><b>RESULTS</b>The secretions of tumor necrosis factor-alpha (TNF-alpha) and interlukine-6 (IL-6) by macrophages co-cultured with the necrotic cells were significantly enhanced as compared with the control cells. The necrotic cells also significantly augmented the secretion of the pro-inflammatory cytokines induced by LPS.</p><p><b>CONCLUSION</b>Necrotic cells not only induces pro-inflammatory cytokine expression by themselves but also work synergistically with LPS to enhance the cytokine production, suggesting the important roles of necrotic cells to initiate and maintain the inflammatory responses.</p>