Biomedical subjects

F Morel

Publications and source records attributed to F Morel.

At least 73 records · Page 4Linked to original sources

PubMed1998

Developmental changes in heteroplasmy level and mitochondrial gene expression in a Drosophila subobscura mitochondrial deletion mutant.

Eighty percent of DNA molecules are deleted in the mitochondrial population of an adult mutant strain of D. subobscura. Both intact and deleted genomes are autonomous monomers. The heteroplasmy level, which is lower in germ tissue, increases from the oocytes (60%) to the third larval instar (83%), and is then maintained throughout the life of the fly. The mtDNA/nuclear DNA ratio is on average two-times greater in the heteroplasmic strain than in the wild-type strain, irrespective of the stage, but the cellular content of mitochondria is elevated only in the embryos and pupae of the mutant strain. The steady state concentrations (SSCs) of the transcripts affected by the deletion are greatly reduced at the larval and adult stages, and less so at the pupal stage of the mutant strain compared with the wild-type. The SSCs of these transcripts are identical in the two strains at the embryonic stage. The fusion transcript, indicating that the deleted genome is expressed, was detected at all stages. The mechanisms involved in the changes in the heteroplasmy level during the course of development and in its maintenance from the third larval instar onwards are discussed.

Animals↗

PubMed1998

Molecular analysis of the chromosomal equipment in spermatozoa of a 46, XY, t(7;8) (q11.21;cen) carrier by using fluorescence in situ hybridization.

The meiotic segregation of a balanced reciprocal translocation (7;8) (q11.21;cen) was analysed by interphase fluorescence in situ hybridization (FISH) on carrier spermatozoa. A dual interphase FISH technique was applied to 34,527 decondensed sperm heads with chromosome-7- and chromosome-8-specific alpha-satellite probes. Analysis with such probes was possible according to the cytogenetic characteristics of these translocation breakpoints, which implied a centromeric breakpoint. The majority of the analysed nuclei (56.70%) showed normal (30.40%) or balanced (26.30%) chromosomal equipment resulting from alternate segregation during meiosis. A total of 14,935 spermatozoa (43.26%) was unbalanced with a predominance of gametes resulting from adjacent-I (25.10%) or adjacent-II (11.10%) segregation; such gametes could produce partial mono- or trisomies at term. The frequency of analysed cells resulting from a 3:1 segregation, which could induce complete mono- and trisomies at term, was 7.06%; 0.04% of scored cells were diploid. The same dual-FISH technique was carried out either with chromosome-15- and chromosome-18-specific probes or with gonosome-specific probes, in order to detect a possible interchromosomal effect. A significant increase of disomic 18 spermatozoa was observed in the carrier. Such studies are not yet frequent. Multicolour-FISH seems a rapid and accurate tool for direct analyses of spermatogenetic segregation mechanisms in a carrier of balanced chromosomal abnormalities and provides interesting information for characterizing the possible risks for the offspring.

Adult↗

PubMed1998

Interindividual variations in the disomy frequencies of human spermatozoa and their correlation with nuclear maturity as evaluated by aniline blue staining.

OBJECTIVE: To evaluate the importance of interindividual variations in the disomy frequencies of human sperm and their possible correlation with the principal semen parameters. DESIGN: Prospective randomized analysis of sperm nuclei by fluorescence in situ hybridization and analysis of semen parameters. SETTING: University-based laboratory for reproductive biology. PATIENT(S): Fifty-seven human ejaculates selected at random from a population of men undergoing semen analysis. INTERVENTION(S): Semen specimens were analyzed, and sperm samples were prepared for fluorescence in situ hybridization. MAIN OUTCOME MEASURE(S): Semen parameters, including necrozoospermia, global motility, sperm concentration, multiple abnormalities index, and teratozoospermia were evaluated, aniline blue staining was completed, and disomy frequencies for chromosomes 8, 15, 18, X, and Y were determined using fluorescence in situ hybridization. RESULT(S): Noticeable differences in disomy frequencies between individuals were observed, and these frequencies were correlated with the degree of nuclear maturity. CONCLUSION(S): We hypothesize that the positive correlation can be explained by an abnormality of chromosomal segregation at the time of meiosis that would cause disturbances during the transition of nucleoprotein or by one or several premeiotic abnormalities of chromatin that would perturb both the meiotic process and the construction of definitive proteins.

Adult↗

PubMed1998

Gelatinase concentration in tears of corneal-grafted patients.

PURPOSE: Gelatinolytic enzymes, which degrade type IV basement membrane collagen, have been shown to be expressed by corneal cells, either constitutively (gelatinase A or MMP-2) or after induction (gelatinase B or MMP-9). Our aim was to determine whether an enhanced MMP-9 and eventually MMP-2 concentration in tears could be evidenced in the case of corneal-graft failure. METHODS: The amount of MMP-2 and MMP-9 gelatinolytic enzymes was measured by quantitative zymography in tears of twenty-one controls (84 samplings) and in tears of twenty-three corneal-grafted patients in a one-year post-graft follow-up study. RESULTS: The mean MMP-2 values in controls were of 8.4 (+/-7.3) pg/10 micrograms protein and the mean MMP-9 values in controls were of 73 (+/-76) pg/10 micrograms protein. No active gelatinase form was detected in any of controls, but in all cases of corneal graft failure, the active forms of both enzymes were present, and enzyme concentrations were higher than control values. All patients had significantly higher MMP-9 values than controls at each sampling time (p < 0.0001). The "corneal-graft failure" patient group had statistically significant higher MMP-9 concentrations in tears than the "successful-graft" patient group at one month (p = 0.0312), four months (p = 0.0158) and one year (p < 0.01) after the graft. The presence of active MMP-9 was highly significant of graft failure four months and one year after the graft (p < 0.0001). In contrast, MMP-2 increase was delayed, with significantly higher MMP-2 values than controls in all patients at four months (p = 0.0231) and one year (p = 0.0001) after the graft, but MMP-2 values could not discriminate between patient groups. CONCLUSIONS: In our study, all cases of graft failure showed abnormally high levels of the active forms of metalloproteinase enzymes, and these values far exceeded the maximum control concentration. MMP-9 measurements in tears made between one and four months after corneal transplantation, and while local corticotherapy is steadily established, should help in predicting corneal graft rejection.

Adult↗

PubMed1998

Matrix metalloproteinase expression in rat pancreatic islets.

Matrix metalloproteinases (MMPs) are involved in the regulation of extracellular matrix turnover and tissue remodeling, through which they can influence the infiltration of a graft by immune-competent cells. Little is known about their role in islet allograft rejection. Therefore we investigated the expression of several MMPs and of two of their tissue inhibitors (TIMPs) in rat pancreatic islets. MMP and TIMP expression in isolated rat pancreatic islets was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) from total RNA. Several MMPs of different substrate specificities were found to be expressed in rat pancreatic islets, either shortly after islet isolation and in all conditions tested (MMP-9, TIMP-1) or after a lag time (MMP-2, MMP-3, MMP-14, TIMP-2). Fetal calf serum induced MMP-7 expression. The inflammatory cytokine interleukin-1 beta (IL-1 beta) did not induce MMP or TIMP expression. We showed that rat pancreatic islets are well equipped with MMPs and TIMPs, but the functional meaning of this expression remains to be elucidated. On the basis of the known effects on tissue remodeling and cytokine processing, we anticipate that they can influence islet engraftment and viability and participate to islet graft rejection.

Animals↗

PubMed1998

Scaffold attachment region-mediated enhancement of retroviral vector expression in primary T cells.

We have studied retroviral transgene expression in primary human lymphocytes. Our data demonstrate that transgene expression is high in activated primary CD4+ T cells but significantly decreased in mitotically quiescent cells. Incorporation of a DNA fragment from the scaffold attachment region (SAR) of the human beta interferon gene into the vector improved transgene expression, particularly in quiescent cells. The SAR element functioned in an orientation-dependent manner and enhanced expression of Moloney murine leukemia virus- and murine embryonic stem cell-based vectors. Clonal analysis of transduced T cells showed that the SAR sequence did not confer position-independent expression on a transgene but rather prevented the decrease of expression when cells became quiescent. The SAR sequence also enhanced transgene expression in T cells generated from retrovirally transduced CD34-enriched hematopoietic progenitor-stem cells in a SCID-hu thymus-liver mouse model. We have used the SAR-containing retroviral vector to express the RevM10 gene, a trans-dominant mutant of the human immunodeficiency virus type 1 (HIV-1) Rev gene. Compared to a standard retroviral vector, the SAR-containing vector was up to 2 orders of magnitude more efficient in inhibiting replication of the HIV-1 virus in infected CD4+ peripheral blood lymphocyte populations in vitro. This is the first demonstration that SAR elements can be used to improve retroviral vector expression in human primary T cells.

3T3 Cells↗

PubMed1998

Inter-regulated balance between gelatinases and tissue inhibitor (TIMP-1) in isolated human glomeruli.

Leukocyte infiltration inside glomeruli necessitates basement membrane collagen i.v. breakdown and leads to mesangiolysis, cell proliferation and extracellular matrix synthesis during the repair process as observed in the course of acute glomerulonephritis, vasculitis and acute graft rejection. Two matrix metalloproteinases, MMP-2 and MMP-9 gelatinases, are expressed and co-secreted in balance with the tissue inhibitor of metalloproteinases-1 (TIMP-1) by activated neutrophils as well as by glomerular cells and are aimed to control basement membrane collage i.v. deposition. Using a conventional double mesh sieving method, pure populations of glomeruli were isolated from fresh human cortex specimen and maintained in short-term cultures. ELISA, zymography and immunoblotting of conditioned serum-free media revealed glomerular MMP-2, MMP-9 and TIMP-1 secretion and activity while reverse transcription-polymerase chain reaction amplification of cellular RNA demonstrated glomerular transcripts coding for these enzymes and their inhibitor. When purified neutrophils were allowed to adhere onto Transwell apparatus in contact with glomerular suspensions, neutrophil 92 kDa gelatinase seemed apparently inhibited mainly because the production of TIMP-1 was enhanced on both sides of the insert. Glomerular 72 kDa and 92 kDa gelatinases were activated shortly (1 to 6 h) after neutrophils had interacted with glomeruli and furthermore upon activation by inflammatory or vasoactive mediators such as phorbol. Decreased neutrophil MMP-9 activity together with reduced MMP-9 mRNA levels and protracted TIMP-1 transcription and secretion during cell-cell interaction could participate to cell detachment from degraded basement membranes and to increased collagen i.v. deposition leading to glomerulosclerosis after initial glomerular injury by inflammatory cells.

Cells, Cultured↗

PubMed1998

Hematopoietic progenitor cells of lymphocytes and dendritic cells.

Lymphocytes and dendritic cells (DCs) are critical for immune responses, yet how they develop from pluripotent hematopoietic stem cells is poorly defined. In humans and mice, it is possible to isolate phenotypically defined subsets of bone marrow (BM) cells that represent intermediate progenitors without long-term repopulating characteristics but with specific lineage differentiation properties. For instance, murine BM CD34+ CD45RA+ cells are progenitors for B and T lymphocytes with no in vivo repopulation activity. In human BM, a small subset (5%) of cells having the phenotype CD34+ Lin- CD10+ CD45RA+ CD38+ Thy-1- c-kit- represents a new class of hematopoietic progenitor cells that gives rise to lymphocytes [T, B, and natural killer (NK) cells] and to DCs but does not produce myeloid or erythroid cells. The identification of such progenitor cells provides the opportunity to define the differentiation and growth requirements for the production of lymphocytes and DCs. Genes involved in lineage specification can also be studied. Altogether, these studies have fundamental implications for understanding the biology of pivotal lineages of immune cells. This understanding could be used to treat a variety of immunodeficiencies and to design novel immunotherapies particularly in the context of hematopoietic cell transplantation.

Animals↗

PubMed1998

Equal distribution of competitive long-term repopulating stem cells in the CD34+ and CD34- fractions of Thy-1lowLin-/lowSca-1+ bone marrow cells.

CD34 antigen is present on most, if not all, human hematopoietic stem cells (HSCs). Consistent with this pattern of expression, we recently reported that primitive murine HSCs defined as competitive long-term repopulating units (CRUs) are highly enriched among CD34+ bone marrow (BM) cells (one CRU/2500 cells). However, in agreement with one recent report that some murine HSCs do not express CD34 (Science 273:242), we observed that 15% of phenotypically defined Thy-1lowLin-/lowSca-1+ (TLS) stem cells were CD34- by fluorescence-activated cell sorting. To examine further the nature of CD34 expression on murine hematopoietic cells, we separated TLS cells into CD34+ (0.022% of BM cells) and CD34- (0.005% of BM cells) fractions, confirmed their phenotype by reverse transcriptase-polymerase chain reaction analysis of CD34 transcripts, and evaluated them in a variety of in vitro and in vivo assays. The CD34+ TLS population contained most (93-95%) of the day 12 spleen colony-forming units (CFU-S) and in vitro colony-forming cells (CFCs). Cobblestone area-forming cells (CAFCs) able to proliferate on a murine bone marrow stromal cell line (SyS-1) represented one of every 5 CD34+ TLS and one of every 31 CD34 TLS cells. When lethally irradiated mice were injected with 100 CD34+ TLS cells, all animals survived and began to recover circulating leukocytes, platelets, and erythrocytes by 15 days. In contrast, only 40% of mice injected with 100 CD34- TLS cells were radioprotected, and hematopoietic reconstitution in surviving mice was not apparent until 21 days. The frequency of CRUs in CD34+ and CD34 TLS cells was determined by injecting limiting numbers of cells into lethally irradiated Ly-5 congenic hosts together with 10(5) "compromised" BM cells to provide radioprotection. CRUs able to regenerate and maintain lymphoid and myeloid cells for at least 6 months in primary and 5 months in secondary hosts represented one of every 156 CD34+ TLS and one of every 35 CD34- TLS cells. However, when normalized for the proportion of TLS cells that were CD34+ or CD34-, it was determined that the recovery of CRU among CD34+ and CD34- TLS cells was equivalent (46% and 54%, respectively). These data are consistent with the previous description of repopulating HSCs among CD34-c-kit+Sca-1+Lin- cells (Science 273:242, 1996) and provide additional evidence that TLS cells are functionally heterogeneous and can be further fractionated on the basis of CD34 expression. Overall, approximately 95% of CFCs, CFU-S, and CAFCs in the TLS population were found to be CD34+, whereas more primitive CRU were distributed equally among CD34+ and CD34 TLS cells. These results should enable better characterization of the most primitive stem cells in murine BM.

Animals↗

PubMed1997

Biochemical and molecular consequences of massive mitochondrial gene loss in different tissues of a mutant strain of Drosophila subobscura.

In the studied mutant strain of Drosophila subobscura, 78% of the mitochondrial genomes lost >30% of the coding region by deletion. The mutations was genetically stable. Despite this massive loss of mitochondrial genes, the mutant did not seem to be affected. Distribution of the two genome types, cell levels of mitochondrial DNA, steady-state concentrations of the mitochondrial gene transcripts, mitochondrial enzymatic activities, and ATP synthesis capacities were measured in the head, thorax, and abdomen fractions of the mutant strain in comparison with a wild type strain. Results indicate that the deleted genomes are detected in all fractions but to a lesser extent in the male and female abdomen. In all fractions, there is a 50% increase in cellular mitochondrial DNA content. Although there is a decrease in steady-state concentrations of mitochondrial transcripts of genes affected by deletion, this is smaller than expected. The variations in mitochondrial biochemical activities in the different fractions of the wild strain are upheld in the mutant strain. Activity of complex I (involved in mutation) nevertheless shows a decrease in all fractions; activity of complex III (likewise involved) shows little or no change; finally, mitochondrial ATP synthesis capacity is identical to that observed in the wild strain. This latter finding possibly accounts for the lack of phenotype. This mutant is a good model for studying mitochondrial genome alterations and the role of the nuclear genome in these phenomena.

Abdomen↗

PubMed1997

Inhibition of cytochromes P-450 and induction of glutathione S-transferases by sulforaphane in primary human and rat hepatocytes.

The isothiocyanate sulforaphane (SF) is thought to be a potential chemoprotective agent. Its effects on Phase I and Phase II enzymes of carcinogen metabolism in primary cultures of rat and human hepatocytes have been investigated. Northern blot analyses of rat hepatocytes showed a dose-dependent induction of mRNAs for rat glutathione S-transferases (rGSTs) A1/A2 and P1 but not M1. This was associated with enhanced levels of not only rGSTA1, A2, A4, A5, and P1 but also of rGSTs M1 and M2. On the other hand, the enzyme activities in rat hepatocytes associated with cytochromes P-450 (CYPs) 1A1 and 2B1/2, namely ethoxyresorufin-O-deethylase and pentoxyresorufin-O-dealkylase, respectively, were decreased in a dose-dependent manner. In SF-treated human hepatocytes, hGSTA1/2 but not hGSTM1 mRNAs were induced, and the expression of CYP1A2 was unaffected, whereas the expression of CYP3A4, the major CYP in human liver, was markedly decreased at both mRNA and activity levels. These observations demonstrate that in intact human and rat hepatocytes, SF may both induce a number of GSTs and cause enzyme inhibition of some but not all CYPs and, in the case of CYP3A4, inhibit both its enzyme activity and its expression.

Adult↗

PubMed1997

Phosphorylation of the respiratory burst oxidase subunit p67(phox) during human neutrophil activation. Regulation by protein kinase C-dependent and independent pathways.

The respiratory burst oxidase of phagocytes and B lymphocytes catalyzes the reduction of oxygen to superoxide anion (O-2) at the expense of NADPH. This multicomponent enzyme is dormant in resting cells but is activated on exposure to an appropriate stimulus. The phosphorylation-dependent mechanisms regulating the activation of the respiratory burst oxidase are unclear, particularly the phosphorylation status of the cytosolic component p67(phox). In this study, we found that activation of human neutrophils with formyl-methionyl-leucyl-phenylalanine (fMLP), a chemotactic peptide, or phorbol myristate acetate (PMA), a stimulator of protein kinase C (PKC), resulted in the phosphorylation of p67(phox). Using an anti-p67(phox) antibody or an anti-p47(phox) antibody, we showed that phosphorylated p67(phox) and p47(phox) form a complex. Phosphoamino acid analysis of the phosphorylated p67(phox) revealed only 32P-labeled serine residues. Two-dimensional tryptic peptide mapping analysis showed that p67(phox) is phosphorylated at the same peptide whether fMLP or PMA is used as a stimulus. In addition, PKC induced the phosphorylation of recombinant GST-p67(phox) in vitro, at the same peptide as that phosphorylated in intact cells. PMA-induced phosphorylation of p67(phox) was strongly inhibited by the PKC inhibitor GF109203X. In contrast, fMLP-induced phosphorylation was minimally affected by this PKC inhibitor. Taken together, these results show that p67(phox) is phosphorylated in human neutrophils by different pathways, one of which involves protein kinase C.

Enzyme Activation↗

PubMed1997

Modulation of glutathione S-transferase subunits A2, M1, and P1 expression by interleukin-1beta in rat hepatocytes in primary culture.

The influence of various cytokines on the expression of glutathione S-transferases (GSTs) was investigated in rat hepatocytes in primary culture. Only treatment of hepatocytes with interleukin-1beta (IL-1) was effective, resulting in a marked decrease in GSTs. Steady-state mRNA levels of rGSTA2 and M1 were strongly down-regulated by IL-1 in a dose-dependent manner after a 24-h exposure while rGSTP1 mRNA level was increased by a 48-h treatment. Similar effects of IL-1 were observed at the protein level. The response to IL-1 appeared to be specific for each subunit within GST gene families. In addition, IL-1 strongly suppressed the induction of rGSTA2 by 3-methylcholanthrene, oltipraz (a synthetic derivative of 1, 2-dithiole-3-thione), and phenobarbital and that of rGSTM1 by oltipraz and phenobarbital, whereas it was ineffective on rGSTP1 induction by these compounds. Using in vitro nuclear run-on transcription assay and Northern blot analysis of alpha-amanitin-treated cells, IL-1-mediated rGSTM1 mRNA decrease was found to result from mRNA destabilization. These results provide the first demonstration that IL-1 regulates some major GST subunits in hepatocytes by a post-transcriptional mechanism.

Animals↗

PubMed1997

Dexamethasone differently modulates TNF-alpha- and IL-1beta-induced transcription of the hepatic Mn-superoxide dismutase gene.

The effects of cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and the synthetic glucocorticoid dexamethasone on the gene expression of antioxidant enzymes have been investigated in rat hepatocytes in primary culture. First, we observed that the hepatocyte culture process induced a strong but transient induction of manganese superoxide dismutase (Mn-SOD) gene expression, whereas copper-zinc superoxide dismutase, glutathione peroxidase and catalase genes were down-regulated. IL-1beta and TNF-alpha both stimulated specifically Mn-SOD gene expression in a time-dependent manner. TNF-alpha rapidly induced Mn-SOD gene expression while IL-1beta was a strong but slow inducer of this gene. Both cytokines acted at the transcriptional level as shown by nuclear run on assays. Dexamethasone prevented the TNF-alpha- but not the IL-1beta induced up-regulation of Mn-SOD gene transcription by a mechanism likely to involve the glucocorticoid receptor. Moreover this glucocorticoid did not suppress the TNF-alpha-induced increase of NF-kappaB binding activity. These results suggest that IL-1beta and TNF-alpha regulate Mn-SOD gene transcription by different pathways.

Albumins↗

PubMed1997

Estimation of aneuploidy levels for 8, 15, 18, X and Y chromosomes in 97 human sperm samples using fluorescence in situ hybridization.

OBJECTIVE: To estimate the mean frequency of aneuploidy levels of chromosomes 8, 15, 18, X, and Y in human sperm, while minimizing the effect of individual factors by analyzing sperm samples from a large set of patients. DESIGN: Prospective randomized analysis of sperm nuclei by fluorescence in situ hybridization. SETTING: University-based laboratory for reproductive biology. PATIENT(S): One hundred two patients with a large distribution of sperm parameters, randomly selected from volunteers who had presented seeking a semen analysis. INTERVENTION(S): The sperm samples were prepared for fluorescence in situ hybridization. MAIN OUTCOME MEASURE(S): The disomy frequencies for chromosomes 8, 15, 18, and sex chromosomes were determined using fluorescence in situ hybridization. RESULT(S): The mean frequencies of disomy for autosomes were 0.18% for chromosome 8, 0.06% for chromosome 15, 0.2% for chromosome 18, and 0.24% for gonosomes (XX, 0.04%; YY, 0.05%; XY, 0.15%). CONCLUSION(S): This study confirms other previous evaluations on restricted numbers of patients. Our results seem to confirm a relative equiprobability of disomy frequencies concerning the different chromosomal pairs during male meiosis.

Adult↗

PubMed1997

Use of hepatocyte cultures for the study of hepatotoxic compounds.

Human and animal hepatocytes in primary culture are widely used in pharmacotoxicological research. They represent a unique in vitro model since they retain both phase I and phase II enzyme activities as well as their inducibility by xenobiotics. Hepatocyte cultures are used for drug screening, identification of the lesions induced by toxic compounds and determination of mechanisms by which xenobiotics exert liver injury.

Animals↗

PubMed1997

The use of primary hepatocyte cultures for the evaluation of chemoprotective agents.

Primary cultures of human and rat hepatocytes are widely used in pharmacotoxicological research. This model presents the advantages of retaining liver function for at least a few days, expressing both phase 1 and phase 2 enzymes, and responding to inducers. Recently we made use of primary hepatocytes to investigate the effects of chemoprotective agents on drug-metabolizing enzyme expression and activities. The treatment of rat and human hepatocytes with two chemoprotective agents, oltipraz (a synthetic derivative of 1,2-dithiole-3-thione) and sulforaphane (an isothiocyanate found in broccoli), clearly demonstrated that both of these compounds are inducers of glutathione transferases and transient inhibitors of cytochrome P450, suggesting that these two compounds could exert their chemoprotective effects by both reducing the formation of reactive metabolites of chemicals and enhancing their inactivation.

Animals↗

PubMed1997

IL-6 and soluble IL-6 receptors (sIL-6R and sgp130) in human pleural effusions: massive IL-6 production independently of underlying diseases.

IL-6, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130) levels were measured in sera and pleural effusions from 42 patients with metastatic carcinoma, non-Hodgkin's lymphoma, tuberculosis, cardiac failure and miscellaneous diseases. Pleural IL-6 levels measured by ELISA were very high in all patient groups (mean 34.8 +/- 15.3 ng/ml) without significant difference according to diseases. IL-6 was shown to be biologically active in a proliferative assay. Serum IL-6 levels were low (0.049 +/- 0.014 ng/ml) and did not correlate with pleural fluid levels. Pleural IL-6 levels correlated with the number of polymorphonuclear cells in pleural fluid (P < 0.03). Pleural sIL-6R levels (76 +/- 8 ng/ml) were always lower than serum levels (196 +/- 12 ng/ml; P < 0.0001) but correlated with them (P < 0.01). Pleural sIL-6R and albumin levels correlated (P < 0.01), suggesting a transudation of sIL-6R from the serum. Pleural sgp130 levels (10.9 +/- 1.0 ng/ml) were lower than serum levels (24.6 +/- 2.8 ng/ml; P < 0.002). After gel filtration of pleural fluid, the bulk of IL-6 (> 90%) was recovered in a 15,000-30,000 fraction, corresponding to the expected mol. wt of free IL-6. These results suggest a production and a sequestration of IL-6 in the pleural cavity in all studied conditions.

Antigens, CD↗