Cigarette smoking and risk of herpes zoster: a population-based cohort study in Taiwan.

The effects of cigarette smoking on the risk of herpes zoster (HZ) infection remain unclear. This study aimed to examine the association between cigarette smoking and HZ. Participants were collected from four rounds (2001, 2005, 2009 and 2013) of the Taiwan National Health Interview Survey. Incident cases of HZ were identified from the Taiwanese National Health Insurance database. Of the 57 641 participants, 3346 developed HZ during the observation period. After controlling for confounders, current smokers had a lower risk of incident HZ than never-smokers (adjusted hazard ratio 0.69; 95% CI 0.62-0.77). There was a trend toward a decreased risk of HZ with increasing numbers of cigarettes per day, years of smoking and cumulative pack-years of smoking among current smokers (Ptrend < 0.001). Former smoking was not associated with risk of HZ. In conclusion, current smoking was significantly associated with a decreased risk of developing HZ.

Cigarette smoking and risk of rosacea: a nationwide population-based cohort study.

BACKGROUND: Most evidence regarding the relationship between cigarette smoking and risk of rosacea is obtained from cross-sectional or case-control studies. OBJECTIVE: To examine the association between smoking and risk of developing rosacea. METHODS: Participants were collected from four rounds (2001, 2005, 2009 and 2013) of the Taiwan National Health Interview Survey. Incident cases of rosacea were identified from the National Health Insurance database. Cox proportional hazard model was used for the analyses. RESULTS: Of the 59 973 participants, 379 developed rosacea during a mean follow-up of 10.8 years. After adjustment for potential confounders, current smokers had a lower risk of rosacea than never smokers [adjusted hazard ratio (aHR) 0.60; 95% confidence interval (CI) 0.39-0.92]. An increase in smoking intensity was associated with a decreased risk of rosacea among current smokers (Ptrend  = 0.0101). Compared with never smokers, current smokers of >15 cigarettes/day had an aHR of 0.51 (95% CI: 0.26-0.99) for rosacea. For incident rosacea, the aHRs (95% CIs) of current smokers of ≤10 years of smoking and ≤10 pack-years of smoking were 0.44 (0.22-0.88) and 0.51 (0.29-0.89), respectively. Former smoking was not associated with rosacea risk. CONCLUSION: Current smoking was significantly associated with a decreased risk of rosacea.

Plasminogen activator inhibitor-1 is associated with leukocyte telomere length in American Indians: findings from the Strong Heart Family Study.

Essentials Plasminogen activator inhibitor-1 (PAI-1) advanced cellular senescence in experiment studies. No population study exists on the association between PAI-1 and biological aging in American Indians. We found cross-sectional and longitudinal associations between higher PAI-1 and shorter telomere length. Our findings suggest a pathway linking PAI-1 with biological aging beyond metabolic factors. SUMMARY: Background Plasminogen activator inhibitor-1 (PAI-1) promotes cellular aging both in vitro and in vivo. Telomere length is a marker of biological aging. Objectives To examine the cross-sectional and longitudinal associations between plasma PAI-1 and leukocyte telomere length in a large-scale epidemiological study of American Indians. Methods We measured leukocyte telomere length (LTL) and plasma PAI-1 in 2560 American Indians who were free of overt cardiovascular disease (CVD) and participated in the Strong Heart Family Study (SHFS) clinical examination in 2001-2003. LTL and PAI-1 were repeatedly measured in 475 participants who attended SHFS clinical visits in both 2001-2003 and 1998-1999. A generalized estimating equation model was used to examine the cross-sectional and longitudinal associations between PAI-1 and LTL, adjusting for known risk factors. Results A higher level of plasma PAI-1 was negatively associated with shorter age-adjusted LTL (ß = -0.023; 95% CI, -0.034 to -0.013). This association was attenuated (ß = -0.015; 95% CI, -0.029 to -0.002) after adjustments for demographics, study site, lifestyle (smoking, drinking and physical activity) and metabolic factors (obesity, blood pressure, fasting glucose, insulin, lipids and kidney function). Further adjustment for hsCRP did not change this association (ß = -0.015; 95% CI, -0.029 to -0.001). Longitudinal analysis revealed that change in plasma PAI-1 was also inversely associated with change in LTL after adjusting for demographics, follow-up years, lifestyle factors, changes in metabolic factors, baseline levels of PAI-1 and LTL (ß = -0.0005; 95% CI, -0.0009 to -0.0001). Conclusions A higher level of plasma PAI-1 was associated with shorter LTL in American Indians. This finding may suggest a potential role of PAI-1 in biological aging among American Indians.

Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China.

We examined the roles of the hepatitis B virus and aflatoxin B1 in the development of primary hepatocellular carcinoma (PHC) in a cohort of 7917 men aged 25 to 64 yr old in southern Guangxi, China, where the incidence of PHC is among the highest in the world. After accumulating 30,188 man-yr of observation, 149 deaths were observed, 76 (51%) of which were due to PHC. Ninety-one% (69 of 76) of PHC deaths were hepatitis B surface antigen (HBsAg) positive at enrollment into the study in contrast to 23% of all members of the cohort (RR = 38.6). Three of the four patients who died of liver cirrhosis also were HBsAg positive at enrollment. There was no association between HBsAg positivity state and other causes of death. Within the cohort, there was a 3.5-fold difference in PHC mortality by place of residence. When estimated aflatoxin B1 levels in the subpopulations were plotted against the corresponding mortality rates of PHC, a positive and almost perfectly linear relationship was observed. On the other hand, no significant association was observed when the prevalence of HBsAg positivity in the subpopulations was compared with their corresponding rates of PHC mortality.

Preserved foods and nasopharyngeal carcinoma: a case-control study in Guangxi, China.

One hundred twenty-eight mothers of nasopharyngeal carcinoma (NPC) cases under age 45 in Yulin Prefecture, China and 174 mothers of population controls were interviewed as part of an epidemiological study to examine childhood exposures in relation to the development of NPC. Exposure before age 2 years to a number of fermented foods was a risk factor for NPC. During weaning, intake of salted fish [relative risk (RR) = 2.6, one-sided P (P) = 0.01], salted duck eggs (RR = 5.0, P = 0.03), salted mustard green (RR = 5.4, P = 0.03), and chung choi (RR = 2.0), P = 0.003), a kind of salted root, was significantly related to an increased risk of NPC. Between ages 1 and 2 years, intake frequency of dried fish [P for linear trend test (linear trend P) = 0.002], fermented black bean paste (linear trend P = 0.0009), and fermented soy bean paste (linear trend P = 0.007) was also positively associated with NPC. A multivariate analysis of these different foods showed all except fermented black bean paste to be independently related to NPC.

A serological case-control study of primary hepatocellular carcinoma in Guangxi, China.

Guangxi is a very high-risk area for primary hepatocellular carcinoma (PHC); the age-standardized (world population) rates for males and females in that Chinese Autonomous Region were 32.5 and 8.5, respectively. Blood specimens from 50 PHC patients and 50 age- and sex-matched controls in Guangxi were analyzed for hepatitis B surface antigen, antibody to hepatitis B surface antigen, and antibody to hepatitis B core antigen. Eighty-six % of cases were hepatitis B surface antigen positive, compared to 22% of controls (relative risk, 17.0). We estimate from the data that persistent hepatitis B virus infection can account for at least 80% of all PHC cases occurring in Guangxi. The consistency of our findings with those from Hong Kong and Taiwan strongly suggests that hepatitis B virus infection is also an important risk factor for PHC in other parts of southern China.

An in vivo effect of the metabolites L-alanine and glycyl-L-leucine on the properties of the lysyl-tRNA synthetase from Escherichia coli K-12. II. Kinetic evidence.

Wild-type Escherichia coli K-12 was grown in minimal medium alone or with the addition of 20 mM L-alanine or 3 mM glycyl-L-leucine. A lysyl-tRNA synthetase mutant strain was grown in minimal medium containing 20mM L-alanine. The lysyl-tRNA synthetase from these strains was purified to 70-90% of homogeneity. Kinetic studies comparing the effect of thermal and urea inactivation on these different lysyl-tRNA synthetase preparations and measurement of the Michaelis constant for lysine and transfer RNA indicated that growth of Escherichia coli in the presence of alanine and glycyl-L-leucine induces an alteration in the properties of the synthetase. Measurement of the apparent Km for ATP at pH 7.25 indicates lysyl-tRNA synthetase has two two binding sites for this substrate, and further studies indicated a dependence of the apparent Km for lysine on the ATP concentration.

An in vivo effect of the metabolites L-alanine and glycyl-L-leucine on the properties of lysyl-tRNA synthetase from Escherichia coli K-12. I. Influence on subunit composition and molecular weight distribution.

Lysyl-tRNA synthetase was purified to 70-90% of homogeneity from Escherichia coli K-12. The enzyme was purified from wild-type cells grown in minimal medium, or minimal medium containing either 20 mM L-alanine or 3 mM glycly-L-leucine. The synthetase was similarly purified from a mutant strain grown in minimal medium plus 20 mM L-alanine. Results based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gel filtration, and trypsin inactivation studies indicate (A) that the presence of L-alanine of glycyl-L-leucine in the culture medium alters the properties of the wild-type enzyme; (B) that the alteration of the synthetase by l-alanine and glycyl-L-leucine is different; and (c) that the molecular weight of lysyl-tRNA synthetase is at least 135000--140000. The results suggest that most likely the metabolites modify the structure of lysyl-tRNA synthetase, but the possibility that the metabolites induce the synthesis of a new lysyl-tRNA synthetase cannot be completely eliminated.

A comparison of isozyme and quantitative genetic variation in Pinus contorta ssp. latifolia by FST.

We employed F-statistics to analyze quantitative and isozyme variation among five populations of Pinus contorta ssp. latifolia, a wind-pollinated outcrossing conifer with wide and continuous distribution in west North America. Estimates of population differentiation (FST) for six quantitative traits were compared with the overall estimate of the differentiation (F*ST) from 19 isozymes that tested neutral to examine whether similar evolutionary processes were involved in morphological and isozyme differentiation. While the FST estimates for specific gravity, stem diameter, stem height and branch length were significantly greater than the F*ST estimate, as judged from the 95% confidence intervals by bootstrapping, the FST estimates for branch angle and branch diameter were indistinguishable from the F*ST estimate. Differentiation in stem height and stem diameter might reflect the inherent adaptation of the populations for rapid growth to escape suppression by neighboring plants during establishment and to regional differences in photoperiod, precipitation and temperature. In contrast, divergences in wood specific gravity and branch length might be correlated responses to population differentiation in stem growth. Possible bias in the estimation of FST due to Hardy-Weinberg disequilibrium (FIS not equal to 0), linkage disequilibrium, maternal effects and nonadditive genetic effects was discussed with special reference to P. contorta ssp. latifolia.

Temporal variation of the mating system in a natural population of jack pine.

Mating system parameters of a northern conifer, Pinus banksiana Lamb., were estimated from allozyme polymorphisms. Seeds analyzed were obtained from serotinous cones of 30 individuals and represented four independent fertilizations in 1975, 1976, 1977 and 1978. Results indicated that a mixed mating system model, with a mean effective outcrossing rate of 88 +/- 0.047%, described the mating system of this stand. However, there was an approximately linear increase in the apparent selfing rate from the oldest (1975) to the newest (1978) crop. Two hypotheses could account for these observations. First, there may have been changes in the mating system during the 4-yr period, but linearity of the differences observed in this study may have been due to chance. These changes were, however, independent of the variability of the observed pollen pool. This indicated that they were not a result of different proportions of outcrossed zygotes directly observed. Second, there could have been a more or less constant amount of selfing, followed by a differential loss of viability of selfed and outcrossed zygotes during the period of storage in the cones. Under this hypothesis, selfed zygotes are at a selective disadvantage relative to outcrossed zygotes. No differences in the mating system could be demonstrated among the three crown strata of this stand. There was significant interlocus heterogeneity in the filial generation genotypic distributions and in the estimated outcrossing rates, reflecting the complex nature of forces that can affect single-locus estimates. There was evidence of some additional inbreeding, possibly due to family structures in the stand; however, this was a minor component of the total inbreeding.

Simple computer quantitation of spleen-to-liver ratios in the diagnosis of hepatocellular disease.

Increased splenic uptake of radiocolloids is a helpful sign in the scintigraphic diagnosis of various hepatocellular diseases, but little attempt has been made to quantify this physiologic phenomenon. We have devised a simple computer method that compares average splenic activity to average right-lobe liver activity. The method is reproducible (r = 0.97) and exhibits little interobserver variation (r = 0.99). One hundred clinically normal subjects were found to have a nearly symmetrical distribution of S/L ratios around a mean of 0.77, with a s.d. of 0.20. Fifteen subjects normal by biopsy were found to have a similar mean spleen-to-liver (S/L) ratio of 0.74. Based upon a normal range of 0.37 to 1.17 (0.77 +/- 2 s.d.), elevated S/L ratios were found in fatty metamorphosis (85%), cirrhosis (67%), and chronic hepatitis (43%). Abnormal S/L ratios in the range from 1.17 to approximately 1.4 were not visually obvious. Overall sensitivity of the S/L ratio in these three diseases is 69%. When combined with the other scintigraphic indications of hepatocellular disease (nonhomogenous colloid uptake, hepatomegaly, splenomegaly, and bone-marrow colloidal uptake), the liver scan was found to have a sensitivity of 93%.

Magnolol protects cortical neuronal cells from chemical hypoxia in rats.

The protective effect of magnolol, a component of Magnolia officinalis, against hypoxia-induced cell injury in cortical neuron-astrocyte mixed cultures was examined. Exposure of the cells to chemical hypoxia (0.5 mM KCN) produced morphological changes in neurons but not in astrocytes. KCN induced dose- and time-dependent increases in release of LDH and decreases in viable cell number. Treatment with magnolol (10 and 100 microM) significantly reduced the KCN-induced LDH release in a concentration-dependent manner. A higher concentration (750 microM) magnolol was toxic. Nuclear condensation was not observed in KCN-treated cells, suggesting that chemical hypoxia-induced cell death was via necrosis, rather than via apoptosis. This is the first report demonstrating that magnolol protects neurons against chemical hypoxic damage or necrotic cell death in cortical neuron-astrocyte mixed cultures.

2-Phenyl-4-quinolone prevents serotonin-induced increases in endothelial permeability to albumin.

To investigate the role of 2-phenyl-4-quinolone in enhancing endothelial monolayer paracellular barrier function and preventing the disturbance of paracellular barrier function by vasoactive agents, the study examined the effect of 2-phenyl-4-quinolone on serotonin-mediated macromolecule transfer and microfilament changes in cultured rat heart endothelial cells. Serotonin-treated endothelial cells induced concentration-dependent increases in the passage of Evans blue dye-bound bovine serum albumin. Incubation of the endothelial monolayers with 2-phenyl-4-quinolone antagonized serotonin- and cytochalasin B-induced macromolecular permeability. 2-Phenyl-4-quinolone also opposed the effect of serotonin or cytochalasin B on the distribution and quantity of actin filaments in the endothelial cytoskeleton. Furthermore, 2-phenyl-4-quinolone alone led to an apparent quantitative increase in F actin fluorescence in endothelial cells. The addition of 10(-7) M 2-phenyl-4-quinolone had an effect on serotonin-induced changes in the myosin and distribution of myosin were comparable to that on serotonin monolayers. In conclusion, 2-phenyl-4-quinolone attenuated the serotonin-induced permeability of rat heart endothelial cells and this was associated with stabilization of F actin microfilaments and changes in the myosin organization. This result suggests that influences on cytoskeletal assembly may be involved in this process.

Decreased protein kinase C activation mediates inhibitory effect of norathyriol on serotonin-mediated endothelial permeability.

We examined the mechanisms of norathyriol on the serotonin-induced increased permeability of rat heart endothelial cell monolayers. The present study showed that the activation of rat heart endothelial cell protein kinase C by phorbol myristate acetate led to the dose-dependent increase in endothelial permeability to albumin, an effect that was inhibited by staurosporine (a protein kinase inhibitor). Staurosporine also attenuated the serotonin-induced increase in permeability. Norathyriol abolished both serotonin- and phorbol myristate acetate-induced permeability. We investigated whether norathyriol, by inhibiting protein kinase C activation, attenuated the serotonin-induced permeability. Immunofluorescence studies demonstrated that norathyriol prevented the redistribution of protein kinase C isozymes following stimulation with serotonin. Western blot analysis showed that norathyriol significantly inhibited the serotonin-induced translocation of the alpha protein kinase C isozyme from the cytosolic to the particulate fraction. In conclusion, norathyriol attenuates the serotonin-induced permeability of rat heart endothelial cells to macromolecules in association with inhibition of protein kinase C activation. This decrease in endothelial cell permeability may be one of the mechanisms for the protective effects of norathyriol against edema formation in response to inflammatory agonists in vivo.

Luteolin-inhibited arylamine N-acetyltransferase activity and DNA-2-aminofluorene adduct in human and mouse leukemia cells.

N-Acetyltransferase enzyme is an important enzyme in the first step of arylamine compounds metabolism. Luteolin has been shown to exit antibacterial and antineoplastic activity. The purpose of this present study is to evaluate the question of whether luteolin could affect arylamine N-acetyltransferase (NAT) activity and DNA-2-aminofluorene adduct formation in human (HL-60) and mouse (L1210) leukemia cells. By using HPLC, N-acetylation of 2-aminofluorene was determined. Luteolin displayed a dose-dependent inhibition to cytosolic NAT activity and intact human and mice leukemia cells. Time-course experiments showed that N-acetylation of 2-aminofluorene measured from intact human and mice leukemia cells were inhibited by luteolin for up to 24 hours. Using standard steady-state kinetic analysis, it was demonstrated that luteolin was a possible uncompetitive inhibitor to NAT activity in cytosols. The DNA-2-aminofluorene adduct formation in human and mouse leukemia cells were inhibited by luteolin. This report is the first demonstration to show that luteolin affects human and mice leukemia cells NAT activity and DNA-2-aminofluorene on adduct formation.

Deficient transforming growth factor beta and interleukin-10 responses contribute to the septic death of burned patients.

In order to understand the roles of pro-inflammatory and anti-inflammatory cytokines in burn injury and sepsis post-burn, serial changes in serum levels of transforming growth factor beta-1 (TGF-beta-1) were determined and compared to those of IL-6 and IL-10 in 15 burned patients. Among these 15 patients, 8 recovered without sepsis. The other seven, who were septic, expired. Our results showed that an initial peak serum TGF-beta-1 response was detected within 1 day post-burn. Peak serum IL-6 and IL-10 responses were also detected within 4 days after the burn injury of these patients. Significant differences in peak serum IL-6, IL-10 and TGF-beta-1 levels were not found between patients with total body surface area (TBSA) of greater or less than 50% and between patients who survived or expired from burn injury. Afterwards, levels of circulating IL-6 and IL-10 remained low in the survivors. However, a second peak response in serum TGF-beta-1 levels was observed in all burned patients analyzed. The second peak serum TGF-beta-1 levels post-burn of the eight survivors and the seven non-survivors were from 28,542 to 76,554 pg/ml (a mean value of 51,256+/-14,264 pg/ml) and from 8616 to 40,851 pg/ml (a mean value of 24,079+/-10,399 pg/ml), respectively. A significant difference (P<0.01) in mean values of the second peak TGF-beta-1 responses between groups of survivors and non-survivors was detected. Levels of circulating IL-6 in the septic non-surviving patients showed a tendency to increase 1-2 weeks post-burn and reached high levels before the expiration of these patients. After an initial peak response, the serum IL-10 level remained low in one of the seven non-survivors, while it increased in the other six non-survivors. However, marked increases in circulating IL-10 levels were observed only just before the death of these non-survivors. In conclusion, an initial increase in serum levels of IL-6, IL-10 and TGF-beta-1 was detected post-burn. A marked increase in serum levels of IL-6 before death suggests its role in the pathophysiology of sepsis in burned patients. In addition, a low secondary TGF-beta-1 response and a lack and/or delay in the increase of circulating IL-10 in the non-survivors may all contribute to the pathophysiology of septic death in burned patients.

Changes in circulating levels of an anti-inflammatory cytokine interleukin 10 in burned patients.

In order to understand the role of an anti-inflammatory cytokine interleukin 10 (IL-10) in the pathophysiology of burn injury, IL-10 levels in serial serum samples of 22 burned patients were analyzed. The total body surface areas (TBSA) of the burn injury ranged from 30 to 90%. Among these 22 patients, 14 recovered and the other eight, who were septic, expired. A significant difference in serum IL-10 values on admission (5-20 h postburn) was found (P<0.05) between patients who survived or died from burn injury as analyzed by the Student's t test. In addition, a significant difference in serum IL-10 on admission was also found (P<0.05) between patients with TBSA of greater or less than 50%. An initial peak serum IL-10 response was detected within 2.5 days postburn. Significant differences in the peak serum IL-10 levels were not found between patients with TBSA of greater or less than 50% and patients who survived or expired from burn injury. Afterwards, serum IL-10 remained low in the survivors, while an increase in serum IL-10 could be detected in the non-survivors with proven sepsis. Levels of circulating IL-6 in these non-surviving patients showed a tendency to increase starting from about 1-2 weeks postburn which coincided temporally with the detection of infections. However, marked increases in circulating IL-10 levels were observed just before death in four of the eight non-survivors. The serum samples of these four patients were collected at 31 h (404.8 pg/ml), 2 h (773.9 pg/ml), 5 days (150.7 pg/ml) and 12 h (177.1 pg/ml) before the expiration of these patients, respectively. IL-10 levels of 28.6, 27. 5 and 13.5 pg/ml were detected in sera of three of the remaining four non-survivors that were collected at 2.5 h, 36 h and 30 h before the expiration of these patients, respectively. There was one non-surviving patient who suffered an 80% burn (patient D4 in Table 1 and Fig. 4) and his IL-10 level at 20 days postburn was 13.4 pg/ml. The serum sample of this patient was collected 22 days before death and he was not suffering from sepsis at this stage. In conclusion, an initial increase in serum levels of IL-10 was detected postburn. A marked increase in serum levels of IL-10 was detected in four of the eight septic patients just before their death. It was considered that a lack and/or a delay in the increase of circulating IL-10 may play a significant role in the pathophysiology of sepsis in burned patients.

Changes in serum tumour necrosis factor-alpha in burned patients.

Dynamic tumour necrosis factor-alpha (TNF-alpha) changes in serial serum samples of 10 burned patients were analysed in this study. The total body surface areas (TBSA) of the burn injury were from 30 to 85 per cent. Among these 10 patients, five recovered and another five died with proved sepsis. On admission which was about 5-13 h postburn, eight of the 10 patients showed their serum TNF-alpha levels to be higher than the mean serum TNF-alpha value of five healthy laboratory personnel. Furthermore, an initial peak serum TNF-alpha response which could be detected within 2.5 days after burn injury has also been observed. However, significant differences in both the serum TNF-alpha values on admission, as well as the first peak serum TNF-alpha levels, were not found (P > 0.05) between patients with TBSA of greater or less than 50 per cent and patients who survived or died from burn injury. In the survivors, serum TNF-alpha stayed at low levels, while it increased markedly in four of the five non-survivors with proven sepsis starting at about 1 week postburn. A significant difference in the maximum serum TNF-alpha levels (P < 0.05) was detected between patients who recovered and died from the thermal injury. In conclusion, great increases in serum TNF-alpha levels have been detected in burned patients with the occurrence of bacterial infection postburn. It is suggested that strategies for the inhibition of TNF-alpha production or in the neutralization of TNF-alpha activity should also be considered in the better treatment of burned patients.

Changes in levels of serum IL-8 in burned patients.

Interleukin (i.l.)-8 levels in serial serum samples of 10 burned patients were analysed. The total body surface areas (TBSAs) of the burn injury ranged 30 to 85 per cent. Of these ten patients, five recovered and the other five, who were septic, died. On admission at about 5-13 h postburn, one of the five survivors and two of the non-survivors had serum IL-8 levels higher than 18.1 pg/ml, which is the detection limit of the IL-8 assay kit. The serum IL-8 values of six healthy laboratory personnel included in the present study were all less than 18.1 pg/ml. Afterwards, an initial peak serum IL-8 response was detected within 2-4.5 days postburn. Significant differences in the peak serum IL-8 levels were not found between patients with TBSAs of greater or less than 50 per cent and patients who survived or expired from burn injury. In the survivors, serum IL-8 remained low, whereas IL-8 increased markedly, starting at about one week postburn in four of the five non-survivors with confirmed sepsis. Significant differences in the maximum serum IL-8 levels were detected between patients who recovered vs. those who died from the thermal injury. In conclusion, the results showed that there was an increase in serum IL-8 postburn. Serum IL-8 was significantly higher in the septic patients, who all died. This cytokine may play a significant role in the pathophysiology of sepsis in burned patients.

Changes in circulating levels of interleukin 6 in burned patients.

Interleukin 6 (IL-6) levels in serial serum samples of 10 burned patients were analyzed. The total body surface areas (TBSA) of the burn injury varied from 30 to 85%. Among these 10 patients, five recovered and the other five, who were septic, expired. A significant difference in serum IL-6 values on admission (5-13 h postburn) was found (p < 0.05) between patients who survived or died from burn injury as analyzed by the Wilcoxon's rank sum test. In addition, a significant difference in serum IL-6 on admission was also found (p < 0.05) between patients with TBSA of greater or less than 50%. Afterwards, an initial peak serum IL-6 response was detected within 4 days postburn. Significant differences in the peak serum IL-6 levels were not found between patients with TBSA of greater or less than 50% and patients who survived or expired from burn injury. In the survivors, serum IL-6 remained low, while IL-6 increased markedly starting at about one to two weeks postburn in four of the five nonsurvivors with proven sepsis. Except for the patient who expired 42 days postburn, the maximum serum IL-6 values of the other four nonsurvivors were all greater than those of the five survivors from burn injury. Significant correlation (p < 0.05) relating the change in serum IL-6 and body temperature was observed in only two (one survivor and one nonsurvivor) of the ten patients. Changes in serum IL-6 were also compared with changes in circulating TNF-alpha and IL-8 determined previously. A similar pattern in the dynamic changes of circulating TNF-alpha, IL-8 and IL-6 was observed in the individual burned patient. An increase in serum levels of all three cytokines was detected postburn. Serum levels of three cytokines were significantly higher in the septic patients, who all died. It was considered that all three cytokines analyzed may play a significant role in the pathophysiology of sepsis in burned patients.