D-Methionine Ameliorates Cisplatin-Induced Muscle Atrophy via Inhibition of Muscle Degradation Pathway.

Cisplatin induces anorexia, weight loss, loss of adipose tissue, skeletal muscle atrophy, and serious adverse effects that can cause premature termination of chemotherapy. The aim of this study was to use an animal model to assess cisplatin therapy (3 cycles) with and without d-methionine to investigate its protective effects on cisplatin-induced anorexia and skeletal muscle wasting. Wistar rats were divided into 3 groups and treated as follows: saline as control (group 1), intraperitoneal cisplatin once a week for 3 weeks (group 2), and intraperitoneal cisplatin once a week for 3 weeks plus oral administration of d-methionine (group 3). Tissue somatic index (TSI), gastric emptying index (GEI), and feeding efficiency were measured. Both hepatic lipid metabolism and muscle atrophy-related gene expressions and C2C12 myotubes were determined by polymerase chain reaction. Micro-computed tomography (micro-CT) was used to conduct assessment of bone microarchitecture indices. Pathological changes of the gastric mucosa were assessed by hematoxylin and eosin staining after euthanizing the animals. d-Methionine increased food intake, weight gain, gastric emptying, and feeding efficiency, as well as decrease stomach contents, after cisplatin injections. Cisplatin caused shortening of myofibers. Cisplatin-induced muscle mass wasting was mediated by the elevation of mRNA expressions of MAFbx and MuRF-1 in ubiquitin ligases in muscle tissue homogenate. The mRNA expressions of MyoD and myogenin, markers of muscle differentiation, declined following cisplatin administration. The administration of d-methionine not only led to significant improvements in myofiber diameter and cross-sectional fiber areas but also reversed muscle atrophy-related gene expression. However, there were no significant changes in stomach histology or microarchitecture of trabecular bone among the study groups. The results indicate that d-methionine has an appetite-enhancing effect and ameliorates cisplatin-induced adipose and muscle tissue loss during cisplatin-based chemotherapy.

Erratum to "Establishment of a Consistent L929 Bioassay System for TNF-α Quantitation to Evaluate the Effect of Lipopolysaccharide, Phytomitogens and Cytodifferentiation Agents on Cytotoxicity of TNF-α Secreted by Adherent Human Mononuclear Cells".

[This corrects the article DOI: 10.1080/09629350123139.].

Association of hypoxia inducible factor-1α polymorphisms with susceptibility to non-small-cell lung cancer.

Hypoxia-inducible factor-1α (HIF-1α) is a key regulator of cellular response to hypoxia and has been suggested to play an important role in tumorigenesis and metastasis. The aim of this study was to investigate the role of HIF-1α-1772 C/T (P582S) and -1790 G/A (A588T) polymorphisms in the susceptibility to and severity of non-small-cell lung cancer (NSCLC). Using a case-control study design and polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis, the allele frequencies and genotype distributions of each single nucleotide polymorphism in 285 NSCLC cases and 300 gender-matched controls were compared. The distribution of the genotype frequencies of HIF-1α-1772 C/T and -1790 G/A were significantly different between the NSCLC and the controls. Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were observed for individuals with HIF-1α-1772 T/T genotype against CC/CT genotypes (an OR of 4.04, 95% confidence interval [CI] = 2.02-8.08, P = 0.0001), and HIF-1α-1790 A/A genotype against GG/GA genotypes (an OR of 4.42, 95% CI 2.22-8.78, P < 0.0001). There were no relationship between HIF-1α-1772 C/T or -1790 G/A allele distribution and disease severity of NSCLC (P > 0.05). However, those patients carrying a HIF-1α-1772 T/T genotype or a HIF-1α-1790 A/A had a tendency toward inferior prognosis compared with other patients.

Association of genetic polymorphisms of CXCL12/SDF1 gene and its receptor, CXCR4, to the susceptibility and prognosis of non-small cell lung cancer.

BACKGROUND: The aim of this study was to evaluate the relations of chemokine CXCL12, previously known as stromal cell-derived factor-1 (SDF1), and its receptor, CXCR4, gene variants on non-small cell lung cancer (NSCLC) risk and disease severity. METHODS: Through a case-control study design, genomic DNA samples of 247 NSCLC patients and 328 age and sex-matched controls were subjected to polymerase chain reaction-restriction fragment length polymorphism analysis. The validity of this technique was proven by direct sequencing of amplified products. Statistical analyses were conducted to explore the contribution of polymorphism of the CXCL12/SDF1 gene and CXCR4, in the susceptibility to and prognosis of NSCLC. RESULTS: Overall, the genotype frequencies of CXCL12/SDF1 gene and CXCR4, were significantly different between lung cancer patients and controls (p<0.0001), and also different between patients with lung cancers of various stages (p<0.0001). Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were seen for individuals with CXCL12/SDF1 AA (an OR of 1.95, 95% CI 1.08-3.50, p=0.018), or CXCR4 TT (an OR of 4.71, 95% CI 1.99-11.2, p<0.0001), and for individuals with both CXCL12/SDF1 AA and CXCR4 TT genotypes (an OR of 12.4, 95% CI 1.56-98.3, p=0.002). The patients carrying a homologous AA genotype at CXCL12/SDF1, or a homologous TT genotype at CXCR4, had a tendency to advanced disease and toward poorer prognoses compared with other patients. CONCLUSION: A significant association between the polymorphisms of CXCL12/SDF1 and CXCR4, and the susceptibility to and prognosis of NSCLC was demonstrated.

Association of polymorphisms in the genes of the urokinase plasminogen activation system with susceptibility to and severity of non-small cell lung cancer.

BACKGROUND: Urokinase plasminogen activating (uPA) system is implicated in neoplastic progression. High tissue levels of uPA system components correlate with a poor prognosis in lung cancer. The present study examined the single nucleotide polymorphisms (SNPs) of uPA and the corresponding receptor, uPAR, for exploring their roles in non-small cell lung cancer (NSCLC). METHODS: The allele frequencies and genotype distributions of uPA rs4065 C/T and uPAR rs344781 (-516 T/C) among 375 NSCLC cases and 380 healthy controls were examined using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis. Putative association between the above SNPs and clinicopathological characteristics of NSCLC were also analyzed. RESULTS: The genotype frequencies of the variant homozygotes of uPA and uPAR were significantly different between NSCLC and control subjects. Significant association was also observed between the examined genotypes and disease stage of NSCLC. Logistic regression analysis revealed that individuals with uPA rs4065 TT genotype have higher odds ratios (ORs) for lung cancer. Whereas, subjects with uPAR-344781 CC genotype have lower ORs for lung cancer. The patients carrying a homozygous TT genotype at uPA rs4065, or at least a T allele at uPAR-344781 (-516), had a tendency to develop advanced disease. CONCLUSIONS: Our results revealed that genetic polymorphisms of the uPA rs4065 C/T and uPAR rs344781 (-516 T/C) were associated with the susceptibility and severity of NSCLC.

Evaluation of serum autoantibody levels in the diagnosis of ovarian endometrioma.

OBJECTIVE: We analyzed autoantibodies against tumor-associated antigens (TAAs) in the serum of patients with endometrioma and healthy controls to determine whether autoantibodies can be accurate biomarkers for the diagnosis of ovarian endometrioma. METHODS: Serum samples were obtained from 56 patients with endometriosis and 66 healthy women who served as normal controls. The titers of antibodies against a panel of eight TAAs were analyzed using enzyme-linked immunosorbent assay. RESULTS: We found that the serum IGFII mRNA-binding protein 1 (IMP1) autoantibody and cyclin B1 autoantibody could discriminate between healthy controls and endometriosis patients (AUC-ROC 0.777; 95% confidence interval [CI] 0.694-0.860, P<0.0005, and AUC-ROC 0.614; 95%confidence interval [CI] 0.513-0.714, P=0.031, respectively). Using 0.073 and 0.007 as the cutoff values for IMP1 and Cyclin B1 autoantibody, respectively, the sensitivity and specificity of IMP1 were 85.7 and 63.6%, respectively. When cylcin B1 was combined with IMP1, the specificity increased to 72.7% and the sensitivity slightly decreased to 83.9%. CONCLUSIONS: Our data suggest that IMP1 alone or combined with cyclin B1 seems to fulfill the requirements of sensitivity and specificity to become a useful clinical biomarker of endometrioma. However, further studies will be required to establish the predictive value and to support the clinical use of IMP1/cyclin B1 in the diagnosis and/or screening of endometriosis.

Systemic and bronchoalveolar cytokines as predictors of in-hospital mortality in severe community-acquired pneumonia.

OBJECTIVES: The aim of this study was to determine whether cytokine expression (interleukin [IL]-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]-alpha), C-reactive protein, and endotoxins on the first day of intensive care unit (ICU) admission are associated with hospital mortality in severe community-acquired pneumonia (CAP). DESIGN: This was a prospective study with bronchoalveolar lavage (BAL) and blood sampling. SETTING: This study was carried out in a 44-bed medical ICU of a 1700-bed university hospital. PATIENTS: Participants included 112 mechanically ventilated patients with severe CAP. INTERVENTIONS: Serum and BAL fluid IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, C-reactive protein, and endotoxins on the first day of ICU admission were obtained. MEASUREMENTS AND MAIN RESULTS: The concentrations of TNF-alpha in BALF and IL-6, IL-8, IL-10, and TNF-alpha in serum were higher in nonsurvivors than in survivor patients with CAP. Of these 112 patients with severe CAP (39%), 44 developed acute respiratory distress syndrome (ARDS); these patients seemed to have higher serum IL-6, IL-8, and IL-10 levels than did the non-ARDS group. Furthermore, in the ARDS population, we found that the endotoxin levels in the BAL fluid were higher in the survival than in the nonsurvival group and BAL fluid concentrations of IL-6, IL-8, and IL-1beta and sera levels of IL-6 and IL-10 were lower in the survival than in the nonsurvival group, and they were associated with a high negative predictive value. CONCLUSIONS: Serum and BAL fluid levels of the studied cytokines on admission may provide valuable prognostic information for patients with severe CAP.

Effects of prone position on inflammatory markers in patients with ARDS due to community-acquired pneumonia.

BACKGROUND/PURPOSE: Acute respiratory distress syndrome (ARDS) is a serious disorder of intensive care unit patients. We evaluated the safety of continuous prone position ventilation (PRONE) and its effects on oxygenation and plasma cytokine concentrations in patients with ARDS caused by severe community-acquired pneumonia (CAP). METHODS: This was a prospective observational clinical study conducted in a respiratory intensive care unit of a 1200-bed medical center in central Taiwan. Twenty-two patients with severe CAP and ARDS were included. They were treated by traditional supine ventilation (SUPINE, n = 11) or PRONE (n = 11) if they met the criteria for ARDS. Patients in the PRONE group were ventilated in prone position continuously for at least 72 hours. Plasma cytokines were collected and analyzed at baseline, 24 hours and 72 hours after enrolment. Serial PaO2/FiO2 and complications were evaluated. RESULTS: Complications associated with PRONE were minor and self-limited. PRONE had higher PaO2/FiO2 ratio than SUPINE did at 48 hours after enrolment. The levels of plasma IL-6 concentration declined significantly with time in the PRONE group (p = 0.011). The levels of plasma IL-6 concentration at enrolment, 24 hours and 72 hours after enrolment also predicted the 14th day mortality of all patients. CONCLUSION: PRONE was a safe and effective maneuver for improving oxygenation in patients with severe CAP and ARDS. PRONE also influenced IL-6 expression in patients with severe CAP.

Association of EcoRI polymorphism of the metastasis-suppressor gene NME1 with susceptibility to and severity of non-small cell lung cancer.

BACKGROUND: Human lung cancer cells with high metastatic potential show reduced expression of the metastasis-suppressor gene NME1. However, the biallelic EcoRI polymorphism of this gene has not been studied in lung cancer. With this allelic association study, we aimed to investigate the impact of polymorphisms of the NME1 gene on the susceptibility to and severity of non-small cell lung cancer (NSCLC). METHODS: Through a case-control study design, genomic DNA samples of 255 NSCLC patients and 303 controls, who were age and sex-matched and recruited from the health check-up unit, were subjected to polymorphism analysis with polymerase chain reaction-restriction fragment length polymorphism technique. The validity of this technique was proven by direct sequencing of polymerase chain reaction products. Statistical analyses were conducted to explore the contribution of polymorphism of the metastasis-suppressor gene NME1 in the susceptibility to and severity of NSCLC. RESULTS: Overall, the genotype frequencies of NME1 gene were significantly different between lung cancer patients and controls (p < 0.0001), and also different between patients with lung cancers of various stages (p < 0.0001). Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were seen in patients homozygous (+/+) for variant allele (an OR of 4.02, 95% CI 2.39-6.76; p < 0.0001). Patients carrying a variant polymorphic homozygote (+/+) also had a tendency to advanced disease (p = 0.001). CONCLUSION: A significant association between the polymorphisms of NME1 gene and the susceptibility to and severity of lung cancer was demonstrated.

Morphological characterization of hantavirus HV114 by electron microscopy.

OBJECTIVE: This study was sought to investigate the propagation and morphogenesis of a new strain of hantavirus, HV114. METHODS: The urine of patient with epidemic hemorrhagic fever was inoculated to Vero E6 cells for the virus isolation. Electron microscopy was used to observe the isolated virus, HV114 and the variation of infected Vero E6 cells. RESULTS: According to our observations, the size (90-120 nm) of HV114 is smaller than that reported previously as 110- 160 nm. While ribosome-like particles associated with virions originating from rodent hantaviruses were not observed in HV114, virion budding was exhibited. It suggests that the dumbbell-shaped particles may generated from the process of virion budding. The budding processes suggest that there are several sites for HV114 assembly and maturation, including the host endoplasmic reticulum-Golgi compartment and the host plasma membranes. CONCLUSIONS: The HV114 isolated from the urine of the patient is differed from other hantaviruses which were isolated from rat organs. HV114 might undergo changes during the viral transmission process from rodents to humans.

Polymorphisms of p53 and p21 genes in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a multifactorial disease influenced by genetic and environmental factors, particularly cigarette smoking. Although cigarette smoke may be directly mutagenic, polymorphisms in the genes controlling acquired somatic mutations may also contribute, at least to some extent, to the observed differing susceptibilities to COPD. To investigate the involvement of genetic polymorphisms of p53 and p21 in the pathogenesis of COPD, the authors performed a case-control study involving 206 subjects with COPD and 210 healthy smokers as control subjects. METHODS: Polymorphisms of p53 and p21 genes were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique on genomic DNA isolated from peripheral lymphocytes. The distribution of the p53 and p21 polymorphisms in healthy subjects and COPD patients was examined and compared using the Pearson X2 test. Significance was accepted at P < 0.05. Odds ratios (ORs) and 95% confidence intervals (CIs) of each specific genotype were calculated using logistic regression analysis to quantitatively assess the degree of association observed. RESULTS: The distribution frequencies of genotypes of p53 codon 72 and p21 codon 31 were significantly different between the COPD and the control groups. Higher ORs for COPD were seen for persons with p53 Pro/Pro or Pro/Arg genotypes against Arg/Arg genotype [OR = 2.35, 95% CI 1.27-4.39, P = 0.008], or p21 Arg/Arg and Arg/Ser genotypes against Ser/Ser genotype [OR = 2.07, 95% CI 1.06-4.05, P = 0.033]. CONCLUSIONS: The polymorphisms of p53 and p21 were significantly associated with the occurrence of smoking-related COPD in Taiwan Chinese patients.

Association of TNF-alpha polymorphism with susceptibility to and severity of non-small cell lung cancer.

BACKGROUND: Genetic polymorphisms in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene are involved in the regulation of expression levels and have been associated with various inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter region of the TNF-alpha gene (-308 G/A and -238 G/A) for their role in the susceptibility to and severity of non-small cell lung cancer (NSCLC), by means of an allelic association study. METHODS: Using a case-control study design, lung cancer patients (n = 202) and appropriate age- and sex-matched controls recruited from the health check-up unit (n = 205) were subjected to genotype analysis for these polymorphisms, using a high-throughput allelic discrimination method. RESULTS: Genotype was analyzed using the polymerase chain reaction-restriction fragment length polymorphism technique with genomic DNA isolated from peripheral blood lymphocytes. Overall, the distribution of the genotype frequencies of TNF-alpha-308 A/G and -238 A/G were significantly different between the lung cancer patients and the healthy controls, and also different between patients with lung cancers of various stages (p < 0.0001). Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were seen for individuals with TNF-alpha-308 AA/GA genotypes against GG genotype (an OR of 3.75, 95% CI 2.38-5.92, p < 0.0001), and lower ORs were seen for individuals with TNF-alpha-238 AA/GA genotypes against GG genotype (an OR of 0.26, 95% CI 0.13-0.50, p < 0.0001). The patients carrying a homologous AA or heterologous GA genotype at TNF-308 (p = 0.017), or a homologous GG genotype at TNF-238 (p = 0.001), had a tendency to advanced disease. CONCLUSIONS: A significant association between the 308 G/A and 238 G/A polymorphisms in the promoter region of TNF-alpha and the susceptibility to lung cancer was demonstrated. Also, these two polymorphisms were associated with the severity of lung cancer. The -308 A allele has a promotive effect for lung cancer development and progression, whereas the -238 A allele has a protective function against lung cancers.

Etiology and cytokine expression in patients requiring mechanical ventilation due to severe community-acquired pneumonia.

BACKGROUND: The relationship between bacterial etiology and serum cytokine levels in patients with severe community-acquired pneumonia (CAP) without response to initial empiric treatment remains unclear. This study investigated the bacterial etiology, outcomes, and bronchoalveolar and systemic cytokines (interleukin [IL]-1beta, IL-8, IL-10) in these patients. METHODS: This hospital-based study enrolled 47 consecutive patients without response to initial empiric treatment and requiring mechanical ventilation due to severe CAP between July 1, 2000 and October 31, 2001, in a respiratory intensive care unit of a 1200-bed teaching hospital in central Taiwan. Bronchoalveolar lavage (BAL) was performed within 3 days after hospitalization. BAL fluid was processed for quantitative bacterial cultures. Blood samples were taken just before BAL, and the levels of both BAL and serum cytokines were measured. RESULTS: The most common pathogens isolated were Pseudomonas aeruginosa (22.5%) and Klebsiella pneumoniae (25%). Patients with a K. pneumoniae isolate (n = 10) had significantly higher levels of IL-1beta in BAL fluid and significantly higher levels of IL-10 in serum and BAL fluid than patients with other etiologies. Non-survivors had higher levels of serum IL-8 (p = 0.001), serum IL-10 (p < 0.001) and BAL IL-10 (p = 0.039) than survivors. Marked increases in local and systemic cytokine expression (IL-8 and IL-10) were noted in rapidly fatal cases. CONCLUSION: P. aeruginosa and K. pneumoniae are the most common causes of CAP requiring mechanical ventilation in Taiwan. Cytokine patterns in the BAL fluid and serum of patients with severe CAP due to K. pneumoniae showed significant elevations compared to other pathogens. Bronchoalveolar and systemic cytokine levels (especially IL-10) predicted mortality. These findings suggest the need for a clinical trial to determine how immunomodulating therapy might affect cytokine profiles and clinical outcome.

The involvement of genetic polymorphism of IL-10 promoter in non-small cell lung cancer.

STUDY OBJECTIVES: Interleukin-10 (IL-10) is mainly an anti-inflammatory cytokine produced by a number of cells including normal and neoplastic cells and has been implicated in autoimmunity, transplantation tolerance and tumorigenesis. Inter-individual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. The aim of this study was to determine whether polymorphisms in the IL-10 gene promoter were involved in predisposing an individual to non-small cell lung cancer (NSCLC). PATIENTS: A total of 154 patients with non-small cell lung cancer were recruited into this study, together with 205 age- and gender-matched healthy smokers acting as control subjects. MEASUREMENTS: Polymorphisms of sites within the promoter region of IL-10 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism technique on genomic DNA isolated from peripheral lymphocytes. The validity of this technique was proven by direct sequencing of polymerase chain reaction products. Statistical analyses were conducted to explore the contribution of polymorphism of IL-10 promoter to the susceptibility to NSCLC. RESULTS: The distribution frequencies of genotypes of IL-10-1082, -819 and -592 were significantly different between NSCLC patients and controls. Pearson chi2 analysis showed that the frequency for IL-10-1082 G allele, IL-10-819C allele and IL-10-592C allele was independently higher in NSCLC patient group than that in the control group. Higher odds ratios (ORs) for NSCLC were seen for individuals with G allele of IL-10-1082 [OR=5.26, 95% CI 2.65-10.4, p<0.0001], C allele of IL-10-819 [OR=1.57, 95% CI 1.15-2.16, p=0.005], C allele of IL-10-592 [OR=1.59, 95% CI 1.15-2.19, p=0.005]. CONCLUSION: The polymorphisms of IL-10 genes were significantly associated with the occurrence of NSCLC.

Evaluation of nuclear matrix protein-22 as a clinical diagnostic marker for bladder cancer.

OBJECTIVES: To evaluate prospectively the prognostic power of urinary nuclear matrix protein-22 (NMP-22) for bladder cancer in Taiwanese screening and surveillance settings. METHODS: Single voided urine samples were obtained from 68 healthy individuals, 303 patients with benign urothelial diseases, and 28 patients with urogenital tumors. The NMP-22 levels in the urine samples were measured using enzyme-linked immunosorbent assay methods. RESULTS: The median NMP-22 level in healthy individuals and patients with benign and malignant disease was 5.9, 4.8, and 7.4 U/mL, respectively. The positive NMP-22 rate in healthy individuals and patients with benign and malignant disease was 4.4%, 17.2%, and 50%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value was 50%, 82.8%, 21.2%, and 94.7%, respectively, using 7.5 U/mL as the cutoff value. CONCLUSIONS: Our data demonstrated that NMP-22 is not a good diagnostic tool for screening or follow-up surveillance of bladder cancer owing to its low sensitivity and positive predictive value. Nevertheless, it could be adopted as a tool to rule out the possibility or risk of developing bladder cancer because of its high negative predictive value in our study.

Alteration of autoantibodies against p53 in Taiwanese lung cancer patients undergoing chemotherapy.

BACKGROUND: Correlation between p53 autoantibodies (p53 Abs) titers and the efficacy of Taiwanese lung cancer patients undergoing chemotherapy has never been investigated. Our present study aimed at evaluating putative possibility of using p53 Abs levels as a model system to monitor effect of chemotherapy and prognosis prediction of lung cancer. METHODS: The prevalence of p53 Abs in lung cancer patients and temporal alteration of p53 Abs titers in lung cancer patients carrying p53 Abs were investigated by using ELISA and Western blot analysis. RESULTS: p53 Abs was detected in 17 of 277 (6.14%) lung cancer patients, the positivity of p53 Abs in patients with small cell lung carcinoma and non-small cell lung carcinoma was 4.88% and 6.36%, respectively. No significant association between p53 Abs and patients' clinical manifestations was found. Titer of p53 Abs was decreased in 6 of 17 p53 Abs-carrying patients after chemotherapy. However, the decreasing p53 Abs titers were not correlated with patients' survival or chemotherapeutic efficacy. CONCLUSIONS: The prevalence of p53 Abs in Taiwanese lung cancer is much lower than that in Caucasians. It is unlikely that p53 Abs titer could be a monitoring indicator for the chemotherapeutic efficacy or a prognosis indicator of lung cancer.

Bronchoalveolar interleukin-1 beta: a marker of bacterial burden in mechanically ventilated patients with community-acquired pneumonia.

OBJECTIVE: To assess the relationship between concentrations of bronchoalveolar cytokines and bacterial burden (quantitative bacterial count) in intubated patients with a presumptive diagnosis of community-acquired pneumonia. DESIGN: A cross-sectional and clinical investigation. SETTING Medical/surgical and respiratory intensive care unit of a tertiary 1,200-bed medical center. PATIENTS: According to the time course of community-acquired pneumonia at the time of study with bronchoalveolar lavage, 69 mechanically ventilated patients were divided into three subgroups: primary (n = 11), referral (n = 23), and treated (n = 35) community-acquired pneumonia. INTERVENTIONS: Bronchoalveolar lavage was performed in the most abnormal area on chest radiograph by fiberoptic bronchoscope. Bronchoalveolar lavage fluid was processed for quantitative bacterial culture. The concentrations of bronchoalveolar lavage cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, and interleukin-10) also were measured. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients had a positive bacterial culture (bronchoalveolar lavage > or = 10 colony-forming units/mL)., and made up 76% of pathogens recovered at high concentrations. The concentrations of bronchoalveolar lavage interleukin-1 beta were 199.1 +/- 32.1 and 54.9 +/- 13.0 pg/mL (mean +/- se) in the patients with positive and negative bacterial culture, respectively (p < .001). Bronchoalveolar lavage interleukin- 1 beta was significantly higher in the patients with a high bacterial burden (p < .001), with mixed bacterial infection (p < .001), and with pneumonia (p < .001), compared with values in patients without these features. The relationship between bacterial load and concentrations of bronchoalveolar lavage interleukin-1 beta was very strong in the patients with primary and referral community-acquired pneumonia but was borderline in treated community-acquired pneumonia. CONCLUSIONS: The common pathogens were similar to the core pathogens of hospital-acquired pneumonia, probably due to antibiotic effects, delayed sampling, and superimposed nosocomial infection. Since the concentration of bronchoalveolar lavage interleukin-1 beta was correlated with bacterial burden in the alveoli, it may be a marker for progressive and ongoing inflammation in patients who have not responded to pneumonia therapy and who have persistence of bacteria in the lung.