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Tuberous sclerosis complex (TSC) is an autosomal dominant disease involving multiple organs, but there are a limited number of reports on family TSC. In the present report, a case of a 52‑year‑old female with a familial genetic TSC, associated with bilateral giant renal angiomyolipoma, was described. The mother, second elder brother and daughter of the patient all exhibited TSC, but the clinical manifestations, and therapeutic prognosis between the family members were not the same. The present case report aimed at identifying an effective diagnostic method and treatment through additional study of familial genetic TSC, in order to prolong and improve the quality of life for patients with TSC. According to the present case and relevant literature reviews, it is suggested that fetal gene detection during pregnancy could prevent the passing of this disease onto further generations. Furthermore, early application of drug treatment may control the development of the disease in diagnosed patients. The combination of classical treatments with a small dose of mammalian target of rapamycin inhibitors is the typical recommendation, which may control the development of the disease more effectively and decrease adverse side‑effects. [ABSTRACT FROM AUTHOR]

It is well known that endurance training is effective to attenuate skeletal muscle atrophy. Succinate is a typical TCA metabolite, of which exercise could dramatically increase the content. The present study aimed to investigate the effect of succinate on protein synthesis in skeletal muscle, and try to delineate the underlying mechanism. The in vitro study revealed that succinate dose‑dependently increased protein synthesis in C2C12 myotube along with the enhancement of phosphorylation levels of AKT Serine/Threonine Kinase 1(Akt), mammalian target of rapamycin, S6, eukaryotic translation initiation factor 4E, 4E binding protein 1 and forkhead box O (FoxO) 3a. Furthermore, it was demonstrated that 20 mM succinate markedly increased [Ca2+]i. Then, the phospho‑extracellular regulated kinase (Erk), ‑Akt level and the crosstalk between Erk and Akt were elevated in response to succinate. Notably, the Erk antagonist (U0126) or mTOR inhibitor (rapamycin) abolished the effect of succinate on protein synthesis. The in vivo study verified that succinate dose‑dependently increased the protein synthesis, in addition to phosphorylation levels of Erk, Akt and FoxO3a in gastrocnemius muscle. In summary, these findings demonstrated that succinate promoted skeletal muscle protein deposition via Erk/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the association between social psychological factors and the occurrence of laryngeal cancer. A 1:1 matched case-control study was conducted. The participants completed questionnaires that included general information, such as the Life Event Scale, the Social Support Rating Scale, and the Eysenck Personality Questionnaire (EPQ). Scores were compared between the groups using paired t-tests and Wilcoxon's signed-rank tests. No significant difference in the psychoticism scale of the EPQ was observed between the two groups (P>0.05). However, significant differences were observed in scores on the life events and social support scales and in the remaining dimensions of the EPQ (all P-values <0.05). Positive life events may be protective factors for laryngeal cancer, whereas reduced utilization of social support may be a risk factor for laryngeal cancer. [ABSTRACT FROM AUTHOR]

Emerging evidence has demonstrated that endoplasmic reticulum stress (ER) is involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the underlying mechanism remains unclear. Viral infection often triggers a hyperinflammatory response by an expansion of the ER. The present study was designed to observe the role of respiratory syncytial virus infection (RSV)-induced ER stress on lung fibrosis. In order to determine the role of ER stress on the onset and progression of pulmonary fibrosis, mice received an intratracheal combined injection of RSV and bleomycin on day 0. At day 7, 14 and 21 following combined injection, RSV in the lung tissues was assayed by immunohistochemistry, cellular classification was assayed by direct microscopic observation after Wright staining and the secretion of cytokines in the broncho-alveolar lavage fluid (BALF) was assayed by ELISA. The expression of collagen type I was assayed by immunofluorescence and western blot analysis. The expression of ER stress related proteins was analyzed by western blot. In addition, the correlations of ER-stress related proteins with collagen type-1 were examined. RSV administration resulted in increased inflammation, as demonstrated by increased levels of leukocytes and pro-inflammatory cytokines in the BALF, and increased collagen type-1 deposition in the lung tissues of bleomycin-induced pulmonary fibrosis animal model at 7, 14 and 21 days. RSV promoted the expression of phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), 78 kDa glucose-regulated protein (GRP78) and activating transcription factor 6a (ATF6a), which accelerated the severity and process of fibrosis in bleomycin-induced animal models. The present study provides evidence that RSV infection accelerated the unfolded protein response and bleomycin-induced lung fibrosis, which may improve our understanding of the pathogenesis of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

In animals, foot-and-mouth disease (FMD) causes symptoms such as fever, limping and the development of blister spots on the skin and mucous membranes. RNA interference (RNAi) may be a novel way of controlling the FMD virus (FMDV), specifically by targeting its cognate receptor protein integrin ß6. The present study used RNAi technology to construct and screen plasmids that expressed small interfering RNA molecules (siRNAs) specific for the integrin ß6 subunit. Expression of green fluorescence protein from the RNAi plasmids was observed following transfection into porcine embryonic fibroblast (PEF) cells, and RNAi plasmids were screened using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. A fragment (5'AAA GGC CAA GTG GCA AAC GGG 3') with marked interference activity was ligated into a PXL-EGFP-NEO integration plasmid and transfected into PEF cells. Transfected cells were selected using G418, and interference of the integrated plasmid was subsequently evaluated by FMDV challenge experiments, in which the levels of viral replication were determined using optical microscopy and RT-qPCR. A total of seven interference plasmids were successfully constructed, including the pGsi-Z4 plasmid, which had a significant interference efficiency of 91.7% in PEF cells (**P<0.01). Upon transfection into PEF cells for 36 h, a Z4 integration plasmid exhibited significant inhibitory effects (**P<0.01) on the integrin ß6 subunit. Subsequent challenge experiments in transfected PEF cells also demonstrated that viral replication was reduced by 24.2 and 12.8% after 24 and 36 h, respectively. These data indicate that RNAi technology may inhibit intracellular viral replication in PEF cells by reducing expression of the FMDV receptor integrin β6. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-1 (MMP-1) has been identified as an important participant in tumor invasion, metastasis and angiogenesis. The purpose of the present study was to investigate the effects of epidermal growth factor receptor (EGFR) localization to lipid rafts on signaling pathways involved in the regulation of MMP-1 expression in SiHa cells, a cervical cancer cell line. EGFR activation by EGF specifically induced MMP-1 expression at both the messenger RNA and protein levels. Additionally, it was observed that EGFR localized to lipid rafts, and that the redistribution of EGFR induced by lipid raft disruption strengthened EGF-induced MMP-1 expression. MMP-1 induction was blocked by the mitogen-activated protein kinase (MAPK) kinase inhibitors PD98059 and U0126. Our results suggested that lipid rafts provide a platform to inhibit EGFR regulation of MMP-1 in SiHa cells through the MAPK/extracellular signal-regulated kinase signaling pathway. [ABSTRACT FROM AUTHOR]

In the present study, adenovirus-mediated interleukin 21 (Ad5-IL-21-EGFP) gene expression was induced in Hepa1-6 cells to investigate whether IL-21 was capable of enhancing antitumor immunity and reducing tumorigenicity of Hepa1-6 in a mouse model. Mice were inoculated intradermally into the right flank with Hepa1-6 cells or Hepa1-6 cells infected with Ad5 or Ad5-IL-21. Four weeks later, the mice were sacrificed humanely, and the tumor volume, tumor weight and mouse spleen index were measured. The levels of IL-21, IL-4 and interferon (IFN)-γ levels in mouse serum and tumor tissues were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Cell counting kit-8 (CCK-8) assay was used to detect the killing ability of spleen T cells and natural killer (NK) cells, and the proliferation ability of T cells. The expression of IL-21 was confirmed by reverse transcription-polymerase chain reaction, western blot analysis and ELISA assay in Ad5-IL-21-EGFP-infected Hepa1-6 cells. The overexpression of IL-21 significantly reduced the tumorigenicity of Hepa1-6 cells. The tumor volumes and tumor weights in Ad5-IL-21-Hepa1-6 mice were much smaller than those in the Ad5-Hepa1-6 group and Hepa1-6 wild-type group. The immunohistochemistry and ELISA assay demonstrated that IL-21 and IFN-γ levels were much higher while the IL-4 level was much lower in the Ad5-IL-21-Hepa1-6 group than in the other two groups. CCK-8 assay revealed that the killing ability of NK cells and T cells, and the proliferation ability of T cells in Ad5-IL-21-Hepa1-6 mice were higher than in the other two groups; the spleen index of Ad5-IL-21-Hepa1-6 mice was also higher than in the other groups. The data had a significant difference (P<0.01). In conclusion, IL-21 reduces tumorigenicity of Hepa1-6 by a mechanism involving enhanced activation of cell-mediated immunity in tumor-bearing mice. [ABSTRACT FROM AUTHOR]

Remodeling of the extracellular matrix (ECM), which is induced by lysyl oxidase (LOX), has been demonstrated to accompany tumor progression; however, the association between LOX expression levels and the malignant behavior of prostate cancer (Pca) remains unclear. The present study aimed to analyze the tumor-associated expression profile of LOX in patients with Pca and to evaluate its potential prognostic value. In the form of a retrospective study, the expression patterns of LOX and collagen I were analyzed in patients with benign prostate hyperplasia and Pca by immunohistochemical examination. The results demonstrated that, with the initiation and progression of Pca, the expression levels of LOX and collagen I were closely associated with Gleason score and tumor stage. In addition, although LOX was expressed in cancer and non-cancer tissues, the differential expression pattern observed in the ECM of Pca cells may indicate that LOX is an important molecule that affects the progression of this disease. Therefore, LOX expression level in the ECM may function as an independent predictor of Pca. [ABSTRACT FROM AUTHOR]

The calcium-sensing receptor (CaSR) releases intracellular calcium ([Ca2+]i) by accumulating inositol phosphate. Changes in [Ca2+]i initiate myocardial hypertrophy. Furthermore, autophagy associated with [Ca2+]i. Autophagy has previously been demonstrated to participate in the hypertrophic process. The current study investigated whether suppression of CaSR affects the hypertrophic response via modulating autophagy. Isoproterenol (ISO) was used to induce cardiac hypertrophy in Wistar rats. Hypertrophic status was determined by echocardiographic assessment, hematoxylin and eosin, and Masson's staining. The protein expression levels of CaSR and autophagy level were observed. Changes of hypertrophy and autophagy indicators were observed following intravenous injection of a CaSR inhibitor. An ISO-induced cardiomyocyte hypertrophy model was established and used determine the involvement of GdCl3. [Ca2+]i was determined using Fluo-4/AM dye followed by confocal microscopy. The expression levels of various active proteins were analyzed by western blotting. The size of the heart, expression levels of CaSR and autophagy level were markedly increased in hypertrophic myocardium. In addition, the present study demonstrated that the indicators of hypertrophy and autophagy were effectively suppressed by CaSR inhibitor. Furthermore, similar effects were demonstrated in neonatal rat hypertrophic cardiomyocytes treated with ISO. It was also observed that CaSR regulates the Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ)-AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling pathway induced by ISO in cardiomyocytes. Furthermore, the AMPK inhibition significantly reduced the autophagy level following CaSR stimulation (P<0.05). The results of the present demonstrated that inhibition of CaSR may ameliorate cardiac hypertrophy induced by ISO and the effect may be associated with the inhibition of autophagy and suppression of the CaMKKβ-AMPK-mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related mortality worldwide. The majority of lung cancers are sporadic, and familial cases are extremely rare. Previous studies have mainly focused on sporadic lung cancer and identified a large quantity of driver genes. However, familial lung cancers are rarer and studied less. The present study recruited a Chinese family in which multiple members had developed lung squamous carcinoma. To find the causative mutations, whole exome sequencing was conducted using a peripheral blood sample of one lung squamous carcinoma patient, and certain variants were validated in more samples. Whole exome sequencing analysis obtained ~2.0 Gb of data (an average of 60x depth for each targeted base), and further validation experiments identified two functional variants in two cancer-related genes (c.1218delA:p.E406fs in PDE4DIP and C1342A:p.L448I in CLTCL1). This study therefore provides useful sources for the further study of hereditary lung cancer. [ABSTRACT FROM AUTHOR]

Primary extragonadal germ cell tumors are rare, and 60% of such cases are seminomas. While the tumors can occur in the mediastinum, thymus, retroperitoneal organs and pineal gland, seminoma originating in the prostate tissue is extremely rare. The present study reports the case of a 54-year-old male with prostate seminoma. The patient was followed up at the First Affiliated Hospital of Dalian Medical University (Dalian, Liaoning, China) from 2001 onwards. The patient received chemotherapy with cyclophosphamide following total resection of the pelvic organs, pelvic lymph node dissection, continent detenial cecum-ascending colic bladder and orchidectomy. The patient experienced considerable post-operative quality of life for >10 years and the disease did not reappear. The study indicated that extragonadal seminoma is sensitive to chemotherapy, and that radical surgery and post-operative adjuvant chemotherapy with cyclophosphamide is a reasonable and feasible treatment method. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most malignant type of human glioma, and has a poor prognosis. Screening differentially expressed genes (DEGs) in brain tumor samples and normal brain samples is of importance for identifying GBM and to design specific-targeting drugs. The transcriptional profile of GSE30563, containing three genechips of brain tumor samples and three genechips of normal brain samples, was downloaded from Gene Expression Omnibus to identify the DEGs. The differences in the expression of the DEGs in the two different samples were compared through hierarchical biclustering. The co-expression coefficient of the DEGs was calculated using the information from COXPRESdb, the network of the DEGs was constructed and functional enrichment and pathway analysis were performed. Finally, the transcription factors of important DEGs were predicted. A total of 1,006 DEGs, including 368 upregulated and 638 downregulated DEGs, were identified. A close correlation was demonstrated between six important genes, associated with immune response, HLA-DQB1, HLA-DRB1, HLA-DPA1, HLA-B, HLA-DMA and HLA-DRA, and the immune response. Allograft rejection was selected as the most significant pathway. A total of 17 transcription factors, including nuclear factor (NF)-κB and NF-κB1, and their binding sites containing these six DEGs, were also identified. The DEGs, including major histocompatibility complex (MHC) class II, DQβ1, MHC class II, DRβ1, MHC class IB, MHC class II, DMα, MHC class II, DPα1, MHC class II, DRα, may provide novel targets for the diagnosis and treatment of GBM. The transcription factors of these six genes and their binding sites may also provide evidence and direction for identifying target-specific drugs. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate changes at the transcript level that are associated with spontaneous astrocytoma progression, and further, to discover novel targets for glioma diagnosis and therapy. GSE4290 microarray data downloaded from Gene Expression Omnibus were used to identify the differentially expressed genes (DGEs) by significant analysis of microarray (SAM). The Short Time Series Expression Miner (STEM) method was then applied to class these DEGs based on their degrees of differentiation in the process of tumor progression. Finally, EnrichNet was used to perform the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis based on a protein-protein interaction (PPI) network. A total of 4,506 DEGs were detected, and the number of DEGs was the highest in grade IV cells (2,580 DEGs). These DEGs were classified into nine clusters by the STEM method. In total, 11 KEGG pathways with XD-scores larger than the threshold (0.96) were obtained. The DEGs enriched in pathways 1 (extracellular matrix-receptor interaction), 3 (phagosome) and 6 (type I diabetes mellitus) mainly belonged to cluster 5. Pathway 2 (long-term potentiation), 4 (Vibrio cholerae infection) and 5 (epithelial cell signaling in Helicobacter pylori infection) was involved with DEGs that belonged to different clusters. Significant changes in gene expression occurred during glioma progression. Pathways 1, 3 and 6 may be important for the deterioration of glioma into glioblastoma, and pathways 2, 4 and 5 may have a role at each stage during glioma progression. The associated DEGs, including SV2, NMDAR and mGluRs, may be suitable as biomarkers or therapeutic targets for gliomas. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate whether microRNA (miR)-185 downregulated androgen receptor expression in the LNCaP prostate carcinoma cell line. Human prostate cancer (PCa) LNCaP cells were cultured and transfected with synthetic has-miR-185 mimic or inhibitor. The transfected cells were subsequently evaluated with a viability assay, nuclear staining, reverse transcription quantitative polymerase chain reaction (RT-qPCR), dual luciferase assay and western blot analysis. The results of the western blot analysis and RT-qPCR indicated that transfection with an miR-185 mimic markedly reduced the androgen receptor (AR) protein expression levels in LNCaP cells, whereas transfection with an miR-185 inhibitor increased the protein expression of AR in the LNCaP cells. The results of the luciferase reporter assay demonstrated that the predicted target site in the AR 3' untranslated regions was a specific functional binding site for miR-185, and that AR was a direct target of miR-185. In addition, downregulation of AR by miR-185 impaired the interaction between AR and androgen response element, and downregulated the expression of the AR target gene prostate specific antigen. Data also suggested that the downregulation of AR mediated by miR-185, inhibited the proliferation and induced the apoptosis of the LNCaP cells. Therefore, the results of the present study suggested that miR-185 may be a potential negative modulator of AR-mediated signaling and may act as a tumor suppressor in prostate cancer cells. [ABSTRACT FROM AUTHOR]

The present study aimed to identify differentially expressed genes (DEGs) regulated by transcription factors (TFs) in glioblastoma, by conducting a bioinformatics analysis. The results of the present study may provide potential therapeutic targets that are involved in the development of glioblastoma. The GSE4290 raw data set was downloaded from the Gene Expression Omnibus database, and consisted of 23 non-tumor samples and 77 glioblastoma (grade 4) tumor samples. Robust Multichip Averaging was used to identify DEGs between the glioblastoma and non-tumor samples. Functional enrichment analysis of the DEGs was also performed. Based on the TRANSFAC® database, TFs associated with the glioblastoma gene expression profile were used to construct a regulatory network. Furthermore, trimmed subnets were identified according to calculated Z-scores. A total of 676 DEGs were identified, of which 190 were upregulated and 496 were downregulated. Gene Ontology analysis demonstrated that the majority of these DEGs were functionally enriched in synaptic transmission, regulation of vesicle-mediated transport and ion-gated channel activity. In addition, the enriched Kyoto Encyclopedia of Genes and Genomes pathway included neuroactive ligand-receptor interaction, calcium signaling pathway, p53 signaling pathway and cell cycle. Based on the TRANSFAC® database, transcriptional regulatory networks with 2,246 nodes and 4,515 regulatory pairs were constructed. According to the Z-scores, the following candidate TFs were identified: TP53, SP1, JUN, STAT3 and SPI1; alongside their downstream DEGs. TP53 was the only differentially expressed TF. These candidate TFs and their downstream DEGs may have important roles in the progression of glioblastoma, and could be potential biomarkers for clinical treatment. [ABSTRACT FROM AUTHOR]

The primary aim of the present study was to evaluate whether maintenance therapy with capecitabine or hormone replacement therapy (HRT) results in improved progression-free survival (PFS) in metastatic breast cancer (MBC) patients who had previously achieved disease control with first-line docetaxel plus capecitabine (TX) chemotherapy. Seventy-nine metastatic breast cancer patients treated between January 2008 and June 2013 with TX chemotherapy were retrospectively analyzed. Following successful initial disease control by the combination chemotherapy, 39 patients received single-agent capecitabine maintenance therapy and 40 patients received HRT as maintenance therapy. The PFS time, objective response rate, clinical benefit rate and safety of the two groups were compared. The median PFS of the total cohort (n=79) was 11.0 months. Furthermore, the median PFS time of the capecitabine (n=39) and HRT groups (n=40) were 10.9 and 11.1 months, respectively (P=0.283). Compared with the PFS time of maintenance treatment only, single-agent capecitabine treatment following TX chemotherapy prolonged the PFS time by 6.8 months and HRT following TX chemotherapy prolonged PFS time by 5.8 months (P=0.551). Of the total cohort, 49 patients did not receive palliative endocrine therapy prior to chemotherapy, including 22 patients in the capecitabine maintenance group and 27 patients in the HRT maintenance group. The PFS time from the commencement of maintenance treatment was significantly different between the two groups, 6.1 months in the capecitabine group compared with 11.5 months in the HRT group (P=0.045). For the 30 patients who underwent palliative endocrine therapy prior to TX chemotherapy, the PFS times of the capecitabine and HRT maintenance treatment groups were 7.5 and 4.1 months, respectively (P=0.043). However, the occurrence of adverse events, such as hematological and gastrointestinal toxicity, as well as hand-foot syndrome, were not significantly different between the two groups. The current study indicated that single-agent capecitabine maintenance therapy may be a potential treatment strategy for MBC patients who responded to capecitabine-based chemotherapy. In particular, capecitabine may provide a more effective maintenance treatment duration compared with HRT for patients who had previously undergone first-line palliative HRT for MBC. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of triptolide on ATP-binding cassette transporter A1 (ABCA1) expression in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. Thirty male Sprague Dawley rats weighing 200-250 g were randomly divided into six groups: Normal (N, n=5), Control (C, n=5), LPS (L, n=5), Triptolide 25 µg (TP1, n=5), Triptolide 50 µg (TP2, n=5) and Triptolide 100 µg (TP3, n=5). The N group was not administered anything; the C group was administered 5 ml/kg normal saline intravenously and 7.5 ml/kg 1% dimethylsulfoxide (DMSO) intraperitoneally; the L group was administered 5 mg/kg 0.1% LPS and 1% DMSO; and the TP1, TP2 and TP3 groups were separately injected with 0.1% LPS and 25, 50 or 100 µg/kg triptolide, respectively. All groups had the same liquid-injection volume. Arterial blood gases, tumor necrosis factor-α (TNF-α) and ABCA1 expression and general pathology were examined following the treatments. It was found that increasing the triptolide dose in the TP1-3 groups resulted in an increase in the expression of ABCA1 mRNA and protein. As compared with the L group, the ABCA1 expression showed a significant increase in TP2 and TP3 groups (P<0.05). In addition, the expression level of TNF-α was significantly increased in the L and TP1 groups, as compared with that in the N or C groups (P<0.05). Conversely, a marked decrease in TNF-α expression was detected in the TP2 and TP3 groups, as compared with the L or TP1 groups (P<0.05). In conclusion, this study found that triptolide could promote the expression of ABCA1 mRNA and protein and inhibit other inflammatory factors during LPS-induced ALI in rats. Regulating the expression of ABCA1 may be one of the protective mechanisms of triptolide. Furthermore, triptolide-induced increases in ABCA1 expression occurred in a dose-dependent manner between 25 and 100 µg/kg. [ABSTRACT FROM AUTHOR]

Pneumonia is a disease causing serious inflammation and infection of the lungs and accounts for >50,000 mortalities annually. The elderly are at an increased risk of developing pneumonia. Pneumonia is more serious in the elderly than in any other age group due to the increased inflammation and risk of community-acquired pneumonia associated with aging. Interleukin-1 receptor antagonist (IL-1RA) is an anti-inflammatory protein that counteracts the destructive effects of inflammatory proteins. Therefore, the possible association between pneumonia in elderly individuals and reduced levels of IL-1RA was investigated in the present study. The number of lymphocytes was counted in all subjects and the relative protein expression levels of IL-1RA were determined using western blot analysis. In addition, the immunological activities of IL-1RA were measured using ELISA. The results demonstrated that the numbers of lymphocytes in the serum and bronchoalveolar lavage fluid (BALF) were significantly higher in elderly patients than those in young patients. Furthermore, the serum and BALF levels of IL-1RA in elderly patients were significantly lower than those in young patients (P<0.05 and P<0.01, respectively). Therefore, reduced levels of IL-1RA in BALF may act as a marker for pneumonia in the elderly and may be a potential adjuvant for the diagnosis of pneumonia in elderly individuals. The results also showed that smoking was associated with significant reductions in the levels of IL-1RA in the BALF of elderly patients. The association between smokers and non-smokers found in this study provides support for the hypothesis that smoking may contribute to the pathogenesis of pneumonia by further reducing IL-IRA levels in certain elderly patients. [ABSTRACT FROM AUTHOR]