板蓝根联合阿奇霉素对小儿支原体肺炎血清炎症因子影响

目的:探究板蓝根联合阿奇霉素对小儿支原体肺炎患者血清中TNF-α、IL-6、IL-8和IL-10浓度的影响。方法:选择2014年1月-2014年12月在我院接受治疗的患儿80例,均确诊为支原体肺炎,按随机数字表分为实验组和对照组。对照组给予阿奇霉素粉针剂与阿奇霉素治疗。实验组在对照组基础上给予板蓝根提取液治疗。观察并比较两组治疗前后外周血TNF-α,IL-6,IL-8及IL-10水平的变化情况及疗效与不良反应发生率。结果:实验组的临床治疗的总有效率较高(P0.05);治疗后两组促炎因子TNF-α、IL-6、IL-8水平均明显下降(P0.05),与对照组相比,实验组TNF-α、IL-6、IL-8水平较低(P0.05);治疗后两组患儿血清抗炎因子IL-10水平均下降(P0.05),与对照组相比,实验组IL-10较低(P0.05);与对照组相比,实验组不良反应发生率较低(P0.05)。结论:板蓝根联合阿奇霉素能够明显降低小儿支原体肺炎患者血清中TNF-α、IL-6、IL-8和IL-10的浓度,提高治疗效果,对临床有指导意义。     

Effect of both ultraviolet B irradiation and histamine receptor function on allergic responses to an inhaled antigen

Exposure of skin to UVB radiation (290-320 nm) modulates the immune system, with most studies showing a suppression of Th1-driven immune responses. This study investigated the effects of UVB on Th2-associated immune responses using a murine model of allergic respiratory inflammation. C57BL/6, histamine receptor-1 knockout (H1RKO), and histamine receptor-2 knockout (H2RKO) mice were exposed to a single 4 kJ/m(2) dose of UVB (twice a minimal edemal dose) on shaved dorsal skin 3 days before intranasal sensitization with papain, a cysteine protease homologue of the dust mite allergen Der p 1. H1RKO mice demonstrated enhanced papain-specific inflammatory responses in the lung-draining lymph nodes (LDLNs), whereas the responses of H2RKO mice closely mimicked those of C57BL/6 mice. UVB irradiation 3 days before sensitization reduced in vitro papain-specific proliferation of LDLN cells of C57BL/6 and H1RKO mice but not H2RKO mice 24 h after challenge. The regulatory effect of UVB was transferred by adoptive transfer of unfractionated LDLN cells from UVB-irradiated, papain-sensitized C57BL/6 and H1RKO donor mice in naive recipients of the corresponding strain that were subsequently sensitized and challenged with papain. Additionally, UVB exposure suppressed papain-induced IL-5 and IL-10 production in vitro by LDLN cells from H1RKO mice but not from C57BL/6 mice or H2RKO mice. The results of this study demonstrate systemic immunomodulation of responses to intranasally delivered Ag by UVB irradiation and implicate a role for the H2 receptor in UVB-induced suppression of Ag-specific responses in the draining lymph nodes.     

The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats.

We have shown that metastasis is suppressed by low-dose total-body irradiation (TBI) in tumor-bearing rats. We have evaluated the immunological effects of low-dose TBI. Total-body irradiation with 0.2 Gy was given 14 days after the implantation of 5 x 10(5) allogenic hepatoma cells (KDH-8) which produce transforming growth factor beta (TGF-beta). On day 21, the splenocytes and tumor-tissue infiltrating lymphocytes were analyzed by FACScan and RT-PCR for the mRNA of the genes that encode tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), TGF-beta, interleukin (IL)-4, IL-10 and IL-6. The same procedure was conducted with untreated rats and with rats that underwent local irradiation with 0.2 Gy. The low-dose TBI significantly decreased the incidence of lung and lymph node metastasis (P < 0.01), whereas the same dose of local irradiation had no effect on the incidence of metastasis. The proportion of CD8+ cells in splenocytes increased in the low-dose TBI group (P < 0.01) compared to the locally irradiated and the untreated groups. The tumor-tissue infiltrating lymphocytes were also significantly increased after low-dose TBI (P < 0.01). The FACScan analysis revealed that 72% of the tumor-tissue infiltrating lymphocytes were CD8+. In both spleen and tumor tissue after low-dose TBI, mRNA expression of the genes that encode IFN-gamma and TNF-alpha increased, while that of the Tgfb gene decreased. There was no expression of the mRNAs of the Il4, Il6 and Il10 genes. CD8+ cells and the cytokine network may play an important role in the antitumor effect of low-dose TBI.     

UVB radiation and its role in the treatment of postmenopausal women with osteoporosis

 In humans, the serum concentration of parathyroid hormone (PTH) is higher in winter than in summer. The increase of PTH can be suppressed by oral vitamin D supplements, which is considered beneficial to those with osteoporosis. The present study investigates whether this effect can also be achieved by serial ultraviolet (UV) irradiation of the skin. In total, 34 women suffering from postmenopausal osteoporosis were included in the open trial. In late winter, 20 patients were irradiated with a spectrum containing UVB, eight times over a period of 4 weeks. The serum concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)₂D], PTH, osteocalcin, alkaline phosphatase (AP), calcium and phosphorus were measured before the first, and 2 days after the last, dose of radiation. The data were compared to the controls (n=14, no UV exposure), who were evaluated once at the start of the study and then again 4 weeks later. After UV irradiation the level of 25(OH)D was increased, whilst that of PTH remained unchanged. The serum level of osteocalcin decreased in the control group, but did not change in the group of women who had been exposed to UV radiation. The present study of osteoporotic women does not confirm previous findings in studies of healthy volunteers i.e. that PTH can be suppressed by exposure to UVB radiation in winter. Further studies are required to specify whether there are subgroups of osteoporotic people who may benefit from exposure to UVB radiation during winter. Received: 31 October 1996 / Accepted: 21 October 1997     

Ultraviolet B radiation induces a transient appearance of IL-4+ neutrophils, which support the development of Th2 responses

UVB irradiation can cause considerable changes in the composition of cells in the skin and in cutaneous cytokine levels. We found that a single exposure of normal human skin to UVB induced an infiltration of numerous IL-4(+) cells. This recruitment was detectable in the papillary dermis already 5 h after irradiation, reaching a peak at 24 h and declining gradually thereafter. The IL-4(+) cells appeared in the epidermis at 24 h postradiation and reached a plateau at days 2 and 3. The number of IL-4(+) cells was markedly decreased in both dermis and epidermis at day 4, and at later time points, the IL-4 expression was absent. The IL-4(+) cells did not coexpress CD3 (T cells), tryptase (mast cells), CD56 (NK cells), and CD36 (macrophages). They did coexpress CD15 and CD11b, showed a clear association with elastase, and had a multilobed nucleus, indicating that UVB-induced infiltrating IL-4(+) cells are neutrophils. Blister fluid from irradiated skin, but not from control skin, contained IL-4 protein as well as increased levels of IL-6, IL-8, and TNF-alpha. In contrast to control cultures derived from nonirradiated skin, a predominant type 2 T cell response was detected in T cells present in primary dermal cell cultures derived from UVB-exposed skin. This type 2 shift was abolished when CD15(+) cells (i.e., neutrophils) were depleted from the dermal cell suspension before culturing, suggesting that neutrophils favor type 2 T cell responses in UVB-exposed skin.     

Experimental study on the possibility of treatment of some hemorrhagic fevers

After intracerebral challenge with 100 PFU of Lassa virus (strain Josiah), all infected mice (CBA/calac) died (control group). Production of pro-inflammatory cytokines (IL-1beta, TNF-alpha) significantly increased in the blood of these mice during the infection. For neutralization of increasing concentrations of these cytokines recombinant IL-1RA was used intraperitonealy at a dose 100 microg kg(-1), everyday, within 5 days from the third day after the challenge. Injections of IL-1RA decreased the concentration of IL-1beta and TNF-alpha and resulted in survival of all infected mice (treatment group). Marburg fever (strain Popp) caused in guinea pigs by 5 LD(50) of virus lead to the significant increase of TNF-alpha in the animal's blood and caused a lethal outcome (control group). Treatment of infected guinea pigs by IL-1RA or anti-TNF serum decreased the concentration of TNF-alpha and resulted in survival of half of the animals (treatment group). For the treatment recombinant IL-1RA was used at a dose 100 microg kg(-1), intramuscularly, everyday, within 6 days from the third day after the challenge or anti-TNF serum, intramuscularly 0.5 ml (2000 U ml(-1); 1 U of the antiserum neutralises 0.03 ng of TNF-alpha), everyday, within 6 days from the third day after the challenge.     

Ultraviolet B Irradiation Reduces the Expression of Adiponectin in Ovarial Adipose Tissues through Endocrine Actions of Calcitonin Gene-Related Peptide-Induced Serum Amyloid A

Ultraviolet (UV) B irradiation decreases blood adiponectin levels, but the mechanism is not well understood. This study investigated how UVB irradiation reduces adiponectin expression in ovarial adipose tissues. Female Hos:HR-1 hairless mice were exposed to UVB (1.6 J/cm²) irradiation and were killed 24 h later. UVB irradiation decreased the adiponectin protein level in the serum and the adiponectin mRNA level in ovarial adipose tissues. UVB irradiation also decreased the mRNA levels of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer binding protein (C/EBP) α, C/EBPβ, and fatty acid binding protein 4 (aP2) in ovarial adipose tissues. In contrast, UVB irradiation increased the mRNA levels of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 in ovarial adipose tissues. In the serum and liver, the levels of serum amyloid A (SAA), involved in PPARγ, C/EBPα, C/EBPβ, aP2, IL-6, and MCP-1 regulation, increased after UVB irradiation. The SAA gene is regulated by IL-1β, IL-6, and tumor necrosis factor-α, but only IL-6 expression increased in the liver after UVB irradiation. Additionally, in the liver, hypothalamus, and epidermis, UVB irradiation increased the expression of calcitonin gene-related peptide (CGRP), which upregulates SAA in the liver. Collectively, our results suggest that the CGRP signal induced by skin exposure to UVB transfers to the liver, possibly through the brain, and increases SAA production via IL-6 in the liver. In turn, serum SAA acts in an endocrine manner to decreases the serum adiponectin level by downregulating factors that regulate adiponectin expression in adipose tissues.     

Changes in serum cytokine levels in active tuberculosis with treatment

It has been reported that IFN-gamma, TNF-alpha, and IL-12 stimulate, and that IL-10, TGF-beta, and IL-4 suppress the protective immune response against tuberculosis. We aim to evaluate changes in the serum levels of pro and antiinflammatory cytokines in active pulmonary tuberculosis (APTB) and the possible effects of treatment on these changes. Serum IL-12p40, IL-4, IL-10, TNF-alpha, IFN-gamma, and TGF-beta1 levels were determined in 20 APTB cases (group 1) before and 2, 4, and 6 months after therapy. The same parameters were also determined in 9 inactive pulmonary tuberculosis (IPTB) cases (group 2) and 9 healthy controls (HC, group 3). Before treatment, the mean serum IFN-gamma, TNF-alpha, and IL-10 levels in group 1 were statistically higher than those in group 2 (P=.001, P=.024, P=.016, resp) or group 3 (P=.003, P=.002, P=.011, resp). The levels in group 1 decreased significantly after treatment (P=.001 for IFN-gamma, P=.004 for TNF-alpha, P=.000 for IL-10). The serum levels of IL-12p40 were significantly higher in group 1 than in group 3 (P=.012) and decreased insignificantly after treatment. There was no difference in serum IL-4 and TGF-beta1 levels among the groups (P>.05). Because the serum IL-12p40, IL-10, TNF-alpha, and IFN-gamma levels were high in APTB, we believe that these cytokines have important roles in the immune response to Mycobacterium tuberculosis (M tuberculosis). These parameters could be used in follow-up as indicators of the success of APTB therapy.     

乌司他丁治疗急性胰腺炎的临床疗效及机制研究

目的:探讨乌司他丁对急性胰腺炎患者的临床疗效及可能机制。方法:收集我院收治的重症急性胰腺炎患者66例,随机分为实验组和对照组。所有患者均给予禁食水、充分补液、纠正电解质紊乱等常规支持对症治疗。对照组予奥曲肽,实验组予乌司他丁,共治疗7天。测定两组患者治疗前、后各血清白介素-6(IL-6)、白介素-8(IL-8)及肿瘤坏死因子-α(TNF-α)水平;治疗前、治疗第1、3天及治疗后进行血常规检测,观察白细胞计数(WBC),并进行血淀粉酶(AMS)、尿淀粉酶(UAMY)测定;分别记录两组患者临床症状及体征恢复时间,判定临床疗效。结果:1治疗后,两组患者血清IL-6、IL-8及TNF-α水平均较治疗前显著下降,且实验组较对照组下降更明显(P0.05);2治疗后,两组患者白细胞计数及血、尿淀粉酶水平均较治疗前明显下降,且实验组较对照组下降更明显(P0.05);3治疗后,实验组各项临床症状及体征消失时间均明显短于对照组(P0.05)。结论:乌司他丁可有效改善急性胰腺胰腺炎患者的各项临床症状,这可能与其显著降低其血清IL-6、IL-8、TNF-α、淀粉酶水平、白细胞计数及尿淀粉酶水平有关。     

Cytokine polymorphisms play a role in susceptibility to ultraviolet B-induced modulation of immune responses after hepatitis B vaccination

UVB exposure can alter immune responses in experimental animals and humans. In an earlier human volunteer study, we demonstrated that hepatitis B-specific humoral and cellular immunity after vaccination on average were not significantly affected by UVB exposure. However, it is known that individuals differ in their susceptibility to UVB-induced immunomodulation, and it was hypothesized that polymorphisms in specific cytokines may play a role in this susceptibility. In this respect, we previously demonstrated that immune responses after hepatitis B vaccination are influenced by the minor allelic variant of IL-1 beta in the general population. For all volunteers, single nucleotide polymorphisms were determined for the following UV response-related cytokines: IL-1 receptor antagonist (+2018), IL-1 alpha (+4845), IL-1 beta (+3953), TNF-alpha (-308), and TNF-alpha (-238). Exposure to UVB significantly suppressed Ab responses to hepatitis B in individuals with the minor variant for the IL-1 beta polymorphism. Increased minimal erythema dose values (just perceptible), which resulted in higher absolute UVB exposures, were observed in the same individuals. There were no associations observed between UVB-induced immunomodulation and the other cytokine polymorphisms examined. This study indicates that individual susceptibility to UVB radiation needs to be considered when studying the effects of UVB in humans.     

肿瘤坏死因子拮抗剂对强直性脊柱炎患者血清相关细胞因子变化的影响及其机制研究

目的:观察肿瘤坏死因子(TNF)拮抗剂对强直性脊柱炎(AS)患者血清中IL-6、IL-17、IL-21、IL-23、TNF-α、TGF-β1表达的影响,结合临床指标的变化探讨肿瘤坏死因子拮抗剂治疗AS的机制与疗效。方法:治疗组应用益赛普联合西乐葆,益赛普25 mg,皮下注射,连用8周,治疗前后评估晨僵VAS评分、腰背痛VAS评分、Bath强直性脊柱炎功能指数(BASFI)及血沉等指标,记录不良反应。用酶联免疫吸附法检测25例肿瘤坏死因子拮抗剂联合COX-2抑制剂治疗前、治疗第4周和治疗8周后AS患者血清中IL-6、IL-17、IL-21、IL-23、TNF-α、TGF-β1的表达情况,检测对照组(20例单独应用COX-2抑制剂的AS患者)治疗前、治疗后的细胞因子水平。结果:肿瘤坏死因子拮抗剂组患者血清中IL-6、IL-17、IL-23、TNF-α的表达在治疗第4周和治疗8周后较本组治疗前及对照组均有明显下降(P0.05);细胞因子IL-21、TGF-β1的表达水平较本组治疗前及对照组无明显降低(P0.05);对照组患者血清中IL-6、IL-17、IL-21、IL-23、TNF-α、TGF-β1的表达在治疗后较治疗前均无明显下降(P0.05);治疗组应用肿瘤坏死因子拮抗剂后较治疗前晨僵及腰背痛VAS评分、BASFI、血沉均显著改善(P0.05),临床疗效优良率为88.0%,对照组优良率为50.0%,有显著差异(P0.05),且治疗组不良反应轻微。结论:肿瘤坏死因子拮抗剂可能是通过降低AS患者血清中一系列细胞因子的表达水平,改善患者的免疫功能及临床症状,延缓了病程进展。但由于病例较少,肿瘤坏死因子拮抗剂联合COX-2抑制剂治疗AS患者的疗效需要在临床中进一步观察。     

Chemopreventive effects of Calluna vulgaris and Vitis vinifera extracts on UVB-induced skin damage in SKH-1 hairless mice

Solar ultraviolet radiation (UV) is a major cause of non-melanoma skin cancer in humans. Photochemoprevention with natural products represents a simple but very effective strategy in the management of cutaneous neoplasia. The study investigated the protective activity of Calluna vulgaris (Cv) and red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on UVB-induced deleterious effects in SKH-1 mice skin. Forty SKH-1 mice were randomly divided into 4 groups (n=10): control, UVB irradiated, Cv + UVB irradiated, BM+UVB irradiated. Both extracts were applied topically on the skin in a dose of 4 mg/40 μl/cm(2) before UVB exposure - single dose. The effects were evaluated in skin 24 hours after irradiation through the presence of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 levels. The antioxidant activity of BM extract was higher than those of Cv extract as determined using stable free radical DPPH assay and ABTS test. One single dose of UVB generated formation of CPDs (p<0.0001) and sunburn cells (p<0.0002) and increased the cytokine levels in skin (p<0.0001). Twenty hours following irradiation BM extract inhibited UVB-induced sunburn cells (p<0.02) and CPDs formation (p<0.0001). Pretreatment with Cv and BM extracts resulted in significantly reduced levels of IL-6 and TNF-α compared with UVB alone (p<0.0001). Our results suggest that BM extracts might be a potential candidate in preventing the damages induced by UV in skin.     

Profiles of pro-inflammatory cytokines in the serum of rabbits after experimentally induced acute pancreatitis

In a recent study we have demonstrated that interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) serum levels correlate positively with the severity of acute pancreatitis (AP), induced by bile acid injected into the pancreatic duct of rabbits. In this article we describe the effect of an IL-10 analogue IT9302 and a monoclonal anti-IL-8 (mon. IL-8) antibody on the content of several pro-inflammatory cytokines in the serum of rabbits, after induction of AP. We found that the serum content of inflammatory cytokines IL-8, IL-1beta, TNF-alpha and monocyte chemoattractant protein 1 (MCP-1) are increased during AP. Injection of IT9302 or mon. IL-8 antibody, diminish the concentration of these cytokines in the serum, with the exception that mon. IL-8 antibody actually increased the circulating level of MCP-1. In addition, intravenous administration of IT9302 increased the serum levels of IRAP, an IL-1beta receptor antagonistic cytokine. Furthermore, intravenous injection of mon. IL-8 antibody increased serum levels of IL-4. It can be concluded that both the human IL-10 analogue IT9302 and mon. IL-8 antibody are able to alter the pro-inflammatory cytokine levels in rabbits suffering from experimentally induced AP.     

耳聋左慈丸对老年肾虚耳聋患者血清TNF-alpha、IL-1beta和IL-6 的影响

目的：探讨耳聋左慈丸对老年肾虚耳聋患者血清TNF-alpha、IL-1beta和IL-6 的影响。方法：选取2014 年4 月至2015 年1 月于我 院以肾虚耳聋为诊断而收入院患者60 例，随机分为实验组和对照组。均给予银杏叶提取物注射液治疗，将10 mL银杏叶提取物 注射液溶于0.9 %氯化钠注射液100 mL，日一次静点；盐酸氟桂利嗪胶囊10 mg，日一次睡前口服，连用14 天为一疗程。实验组在 此基础上加用耳聋左慈丸一次8 丸，一日3 次口服，14 天为一疗程。治疗后通过电测听对患者治疗前后耳聋等级进行测定；并分 别于患者治疗前、治疗第7 天、第14 天采静脉血5 mL，离心取血清，用ELISA 法测定TNF-alpha、IL-1beta和IL-6。结果：①治疗后两组 进行电测听，耳聋等级测定均较治疗前改善，分级呈整体性下降，说明患者耳聋程度经治疗均有所好转，但实验组与对照组相比， 改善更为明显，差异有统计学意义（P＜0.05）；②治疗后第7、14 天，实验组与对照组TNF-琢、IL-1茁和IL-6 均呈逐渐下降趋势，差 异有统计学意义（P＜0.05），相比于对照组，实验组TNF-alpha、IL-1beta和IL-6 下降趋势更为明显，差异有统计学意义（P＜0.05）。结论： 耳聋左慈丸可明显改善老年肾虚耳聋患者耳聋等级以及血清TNF-alpha、IL-1beta和IL-6 水平，对临床具有指导意义。     

紫外辐射对铜绿微囊藻中类菌孢素氨基酸(MAAs)的诱导效应

用8 w紫外灯,距离藻10 cm,以5 min/d、10 min/d、20 min/d连续照射6 d的间断处理和连续照射1 h、1.5 h、2 h、3h、6 h、12 h的连续处理两种方式处理铜绿微囊藻,测得水溶性色素提取液在200~400 nm间的吸收光谱与对照组相比较,没有产生新的吸收峰,说明MAAs的产生不需要紫外线的诱导。同时随着紫外辐射剂量的增加,MAAs的含量先增加,当达到一定的辐射剂量之后,MAAs的含量随着紫外辐射剂量的增加而减小。     

Adaptation to the UV-induced suppression of phagocytic activity in murine peritoneal macrophages following chronic exposure to solar simulated radiation.

Exposure of certain strains of mice to ultraviolet radiation (UVR) is known to suppress both local and systemic immune responses, including a reduction in the phagocytic activity of peritoneal macrophages. However, in many instances, the immunological effects have been observed following a single or a limited number of doses of UVR from sources containing a higher proportion of UVB than that emitted by the sun. The first aim of the present study was to establish whether a single exposure of C3H/HeN mice to solar simulated radiation (SSR) suppressed the ability of the peritoneal macrophages to phagocytose opsonised sheep red blood cells. The mice were irradiated with SSR from Cleo Natural lamps and a single dose of 31.9 J cm(-2) was found to be the minimal dose for significant suppression of macrophage phagocytic activity. Such a dose did not modulate the surface expression of I-A(k), CD11b, CD86 or FcgammaRII/III (CD32/16) on the macrophages. The second aim was to assess whether repeated SSR exposures with a dose below the minimal immunosuppressive dose affected macrophage activity and, if so, to test for photoadaptation by repeated exposures followed by a single, normally immunosuppressive dose of SSR, and then assaying the macrophage activity. Groups of mice were irradiated on each of 2, 10 and 30 days with 14.9 J cm(-2) SSR, followed in some instances by a single additional exposure of 31.9 J cm(-2) on the same day as the last irradiation. The phagocytic activity of the peritoneal macrophages was tested 24 h later. It was reduced by 32%, 18% and 4% respectively after 2, 10 and 30 repeated exposures to SSR, and by 39%, 21% and 7% respectively after 2, 10 and 30 repeated exposures plus the additional higher dose at the end. Thus, although the macrophage activity was initially suppressed by the SSR, photoadaptation of this immune parameter occurred following repeated exposures.     

Interleukin 10 mitigates the development of the zymosan-induced multiple organ dysfunction syndrome in mice.

We investigated the effect of interleukin 10 on the development of zymosan-induced multiple organ dysfunction syndrome (MODS) and on plasma concentrations and production capacity of tumour necrosis factor (TNF)-alpha by peritoneal cells. Groups of C57BL/6 mice received a single intraperitoneal injection with zymosan, a cell wall component of Saccharomyces cerevisiae, at day 0. Daily doses of human recombinant interleukin 10 (IL-10: 10 or 50 microg/kg) were given intraperitoneally either starting directly before administration of zymosan (day 0), or 5 or 8 days after administration of zymosan. The animals were monitored for survival, condition, body weight and temperature. On day 12 all surviving animals were killed to obtain plasma, organs and peritoneal cells. Plasma concentrations of TNF-alpha and lipopolysaccharide-stimulated production of TNF-alpha by peritoneal cells were measured; organ weights were registered as an indicator for organ damage. IL-10 improves survival and clinical condition and also reduces organ damage, but only at the highest dose used and only when started simultaneously with the administration of zymosan. Circulating TNF-alpha concentrations 12 days after zymosan are not affected by any of the IL-10 schedules used. However, lipopolysaccharide-stimulated production of TNF-alpha by peritoneal cells is increased, in a dose- and time-dependent fashion. The anti-inflammatory cytokine IL-10 is able to attenuate the development of MODS in this model, but only when given simultaneously with zymosan, and in high dosages.     

UVB irradiation suppresses cytokine production and innate cellular immune functions in mice

We examined whether ultraviolet-B (UVB) irradiation (6 kJ/m2) alters cytokine production and other innate immune reactions by murine peritoneal macrophages and peripheral neutrophils. Along with these experiments, serum IgG levels were also assessed. In addition, using scanning electron microscopy (SEM) we observed macrophages that had been exposed to UVB in vitro. Results showed that UVB irradiation: (1) decreased IL-12 production while increasing IL-1alpha secretion from macrophages, but had no effect on IL-1alpha from neutrophils; (2) suppressed phagocytosis of macrophages but not of neutrophils; (3) diminished active oxygen production of macrophages but not of neutrophils; (4) had no effect on serum IgG levels; and (5) caused significant cell destruction of macrophages in vitro. These results suggested: (1) that UVB irradiation could induce characteristic suppression of innate immunity; (2) that innate cellular immunity was more susceptible to the effects of UVB irradiation than humoral immunity.     

The time course of inflammatory cytokine secretion in a rat model of postoperative pain does not coincide with the onset of mechanical hyperalgesia

We characterized the time course of inflammatory cytokine release at the site of injury and in plasma after surgery on the rat tail. Anesthetized Sprague-Dawley rats had a 20 mm long incision made through the skin and fascia of their tails. Control rats were anesthetized, but no incision was made. Blood and tissue samples were taken 2 h and 1, 2, 4, and 8 days after surgery and analysed by ELISA for interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In another group of rats, daily behavioral measurements were made of the rats' responses to a blunt noxious mechanical stimulus (4 Newtons) applied to their tails. Primary hyperalgesia developed within 2 h of surgery and lasted for 6 days. The tissue concentrations of IL-1beta, IL-6, and CINC-1 increased within 24 h of surgery, and TNF-alpha concentration increased within 48 h of surgery. Thereafter, cytokine concentrations remained elevated for 4 (IL-1beta and IL-6) to 8 days (CINC-1, TNF-alpha) after surgery. Control animals did not develop hyperalgesia and no changes in cytokines concentrations were detected. Thus, in our model of postoperative pain, secretion of inflammatory cytokines IL-1beta, IL-6, TNF-alpha, and CINC-1 was not essential for the initiation of postoperative hyperalgesia.     

Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response

PFAPA syndrome is characterized by periodic episodes of high fever, aphthous stomatitis, pharyngitis, and/or cervical adenitis. It is of unknown etiology and manifests usually before 5 years of age. We determined serum and intracellular cytokine levels in six PFAPA patients (4 males, 2 females, mean age 8 years (+/- 1.2 SEM), range 4-13) during the symptom-free period as well as 6-12 hours and 18-24 hours after fever onset. Values were compared to age-matched, healthy controls. Febrile PFAPA attacks led to a significant increase in IL-6 and IFN-gamma serum concentrations compared to symptom-free periods and to controls, with IL-1beta, TNF-alpha and IL-12p70 levels being significantly higher than in controls. Lymphocytic IFN-gamma and CD8+ IL-2 production was consistently significantly elevated compared to healthy children. During the asymptomatic period, serum concentrations of IL-1beta, IL-6, TNF-alpha and IL-12p70 were significantly increased compared to controls. Intracellular TNF-alpha synthesis was not elevated at any time point. Soluble TNFRp55 levels were even lower in between febrile episodes, reaching values comparable to controls during attacks, whereas soluble TNFRp75 levels increased during attacks compared to healthy children. Anti-inflammatory IL-4 in serum was at all times lower in PFAPA patients compared to controls with no difference in levels of intracellular IL-4 and IL-10 or serum IL-10. The observed increase of pro-inflammatory mediators, even between febrile attacks, suggests a dysregulation of the immune response in PFAPA syndrome, with continuous pro-inflammatory cytokine activation and a reduced anti-inflammatory response.