Pleural Cavity Of Patients Research Articles

Regulation of ICAM-1 in human neutrophils

Abstract Intercellular cell adhesion molecule 1 (ICAM-1) is a cell surface glycoprotein with a vital role in the immune response to pathogens. The expression pattern of ICAM-1 is wide ranging, encompassing endothelial cells, epithelial cells, and neutrophils. Recent work has characterized the role of ICAM-1 in murine neutrophils, but the function of human neutrophil ICAM-1 is incompletely understood. Herein, we investigated the expression and role of ICAMs in human neutrophils in vitro and in vivo. Our findings show clear expression of ICAM-1, -3, and -4 on peripheral blood–derived neutrophils and demonstrate that the pathogen-associated molecular pattern lipoteichoic acid is an inducer of ICAM-1 expression in vitro. In vivo, neutrophils obtained from the pleural cavity of patients with a parapneumonic effusion display enhanced expression of ICAM-1 compared with peripheral blood– and oral cavity–derived neutrophils. Moreover, migration of peripheral blood–derived neutrophils across endothelial cells can upregulate neutrophil ICAM-1 expression. These findings indicate that pathogen-associated molecular patterns and/or cytokines, alongside transmigration, enhance neutrophil ICAM-1 expression at sites of inflammation. Mechanistically, we observed that ICAM-1high neutrophils display elevated S. aureus phagocytic capacity. However, unlike murine neutrophils, ICAM-1 intracellular signaling in human neutrophils was not essential for phagocytosis of Staphylococcus aureus and reactive oxygen species generation. Taken together, these results have important implications for the regulation of neutrophil-mediated pathogen clearance.

Engineered lactococcus lactis intrapleural therapy promotes regression of malignant pleural effusion by enhancing antitumor immunity

Intrapleural immunotherapies have emerged as a prominent field in treating malignant pleural effusion (MPE). Among these, bacteria-based intrapleural therapy has exerted an anti-MPE effect by immuno-stimulating or cytotoxic properties. We previously engineered a probiotic Lactococcus lactis (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 and co-stimulator OX40 ligands. FOLactis activates tumor antigen-specific immune responses and displays systemic antitumor efficacy via intratumoral delivery. However, no available lesions exist in the pleural cavity of patients with MPE for intratumoral administration. Therefore, we further optimize FOLactis to treat MPE through intrapleural injection. Intrapleural administration of FOLactis (I-Pl FOLactis) not only distinctly suppresses MPE and pleural tumor nodules, but also significantly extends noticeable survival in MPE-bearing murine models. The proportion of CD103+ dendritic cells (DCs) in tumor-draining lymph nodes increases three-fold in FOLactis group, compared to the wild-type bacteria group. The enhanced DCs recruitment promotes the infiltration of effector memory T and CD8+ T cells, as well as the activation of NK cells and the polarization of macrophages to M1. Programmed death 1 blockade antibody combination further enhances the antitumor efficacy of I-Pl FOLactis. In summary, we first develop an innovative intrapleural strategy based on FOLactis, exhibiting remarkable efficacy and favorable biosafety profiles. These findings suggest prospective clinical translation of engineered probiotics for managing MPE through direct administration into the pleural cavity.

FEATURES OF PLEURAL CAVITY DRAINAGE IN PATIENTS WITH ACUTE NONSPECIFIC PLEURAL EMPYEMA

Most authors considered pleural cavity drainage to be the main method of treatment of acute pleural empyema using minor surgery. Despite the simplicity of drainage of the pleural cavity, the number of complications after this surgical manipulation, according to the reports of some authors, varies from 3 to 8 %. The complications of pleural drainage in the patients with acute nonspecific pleural empyema have been studied and the technique of pleural drainage "blindly" has been introduced, which allows drainage to be located along the chest wall. At the first stage of the four−stage study, the complications of pleural drainage in 38 patients with acute nonspecific pleural empyema were analyzed, at the second stage a device for drainage of the pleural cavity "blindly" was developed to place drainage in parallel to the chest wall, at the third stage patients were tested; on IV −− drainage of the pleural cavity of 34 patients was performed according to the proposed method. The reason for the development of drainage complications in the pleural cavity of patients with acute pleural empyema was the inadequate location of drainage in the pleural cavity, drainage of the pleural cavity was carried out in general hospitals without the use of thoracoscopic equipment. Curved thoracoport with trocar for a blind drainage of the pleural cavity "blindly" was developed and introduced into clinical practice. This technique eliminates the involuntary location of the drainage in the pleural cavity, installing it along the chest wall, and is safe. Complications associated with drainage of the pleural cavity according to the developed method using a curved thoracoport with a trocar, inadequate location of drainage, were not observed in patients. Key words: acute pleural empyema, pleural cavity drainage, curved trocar.

A mass originating from chronic pyothorax in the pleural cavity

A 71-year-old male with a past history of tuberculous pleuritis was referred to our hospital in 2008 because of right chest pain. Chest computed tomography (CT) demonstrated a huge mass originated from chronic pyothorax in the right pleural cavity, invading the chest wall. 2-[F]fluoro-2-deoxy-D-glucose Positron Emission Tomography (FDG-PET) imaging showed strong uptake only in the tumor of the right chest wall (Image 1A). Immunohistochemical staining and Southern blot hybridization of biopsied specimens revealed that the diagnosis was CD20 negative pyothorax-associated diffuse large B cell lymphoma. In situ hybridization for Epstein-Barr virus (EBV) disclosed EBV-encoded small RNA expression in the lymphoma cells. Clinical stage was IE, and international prognostic index was low intermediate. First, three courses of pirarubicin-cyclophosphamide, vincristine, prednisolone (COP) were administered. Then confirming that FDG-PET became negative (Image 1B), involved-field radiotherapy of 50 Gy was added. No sign of relapse has been found for more than 2 years. Pyothorax-associated lymphoma (PAL) is defined as nonHodgkin’s lymphoma of exclusively B-cell phenotype developing in the pleural cavity of patients with chronic pyothorax [1,2]. Most of PAL cases express CD20; however, there are a small proportion of cases which do not express B cell antigens such as CD20 and CD79a [3,4]. It is suggested that PAL is strongly associated with EBV [5,6]. A mass in the pleural cavity with a history of tuberculosis should cause one to consider PAL in the differential diagnosis.

Extrapleural pneumonectomy for pyothorax-associated lymphoma

Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma that occurs in the pleural cavity of patients with a long-standing history of pyothorax. Here, we report a left pleuropneumonectomy performed for PAL in a 76-year-old male patient with a 60-year history of pyothorax due to tuberculosis.

Condensin mutations and abnormal chromosomal structures in pyothorax‐associated lymphoma

Transfer of genetic information during mitosis is accurately conducted by proper condensation and segregation of chromosomes, for which condensins play a central role. Both condensin I and II have common structural maintenance of chromosomes subunits, named hCAP-C and hCAP-E. Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma developing in the pleural cavity of patients with long-standing pyothorax. Mutations of hCAP-C and hCAP-E were investigated in 24 leukemia-lymphoma cell lines including eight PAL cell lines, and their influences in chromosome morphology were evaluated. Heterozygous point mutations within hCAP-C were found in two PAL cell lines and corresponding tumor samples (OPL-3 and OPL-7). Deletion of exon 24 within hCAP-E and a point mutation at the donor splice site of intron 24 were detected in OPL-5 and original tumor samples. OPL-5 showed an extensive reduction in expression of not only hCAP-E but also hCAP-C proteins. OPL-5 occasionally showed the chromosome bridge in anaphase and telophase, indicating that segregation is not accurate. OPL-7 showed reduced hCAP-C protein expression, abnormality in chromosome length and width, and abnormal aggregates of hCAP-C protein. These findings indicated that condensin gene alteration might play a role in genome instability, which accelerates the accumulation of other gene alterations in PAL.

Loss of expression of Epstein‐Barr virus nuclear antigen‐2 correlates with a poor prognosis in cases of pyothorax‐associated lymphoma

Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma, which develops in the pleural cavity of patients who have had pyothorax for over 20 years, and is strongly associated with Epstein-Barr virus (EBV) infection. The expression of latent genes, especially EBV nuclear antigen-2 (EBNA-2), influences the growth characteristics and malignant features of EBV-infected cells. Here, the effect of EBNA-2 expression on clinical features was examined in 13 cases of PAL. The EBNA-2 transcript was detected in 8 cases but was absent in 5. There was a significant difference in survival between patients with the transcripts and those without: the 1-year survival rate was 87.5 and 0%, respectively (p < 0.01). There was a discrepancy between EBNA-2 expression and EBNA promoter usage in 6 cases. The Cp/Wp promoter was used in 3 EBNA-2-negative cases, whereas the Qp promoter or multiple promoters were used in 3 EBNA-2-positive cases. Analysis of PAL cell lines provided a clue as to the mechanism underlying the discrepancy between EBNA-2 expression and EBNA promoter usage. Loss of EBNA-2 expression, irrespective of the latency pattern, is correlated with a poor prognosis, suggesting that down-regulation of the EBNA-2 expression could be selection pressure for the progression of PAL.

Pyothorax-Associated Lymphoma

Pyothorax-associated lymphoma (PAL) is a non-Hodgkin lymphoma of exclusively B-cell phenotype developing in the pleural cavity of patients after more than 20-year history of pyothorax resulting from an artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. The most common symptoms on admission are chest pain and fever. Serum neuron-specific enolase level suggesting a diagnosis of small cell lung cancer is occasionally elevated. Histologically PAL usually shows a diffuse proliferation of large cells of B-cell type (diffuse large B-cell lymphoma [DLBL]). In PAL cells, representative B-cell markers other than CD20 are frequently negative with aberrant expression of T-cell markers such as CD2. A gene expression profile of PAL is distinct from nodal DLBL in its higher expression level of interferon-inducible genes. PAL is strongly associated with Epstein-Barr virus (EBV) infection with expression of EBV latent genes such as EBNA-2, LMP-1, together with EBNA-1. Taken together, PAL is a distinct entity both in its clinicopathologic presentation as well as its gene expression profile. Use of an artificial pneumothorax, EBV infection, and cytokines and reactive oxygen species produced in longstanding pyothorax might be important factors for PAL development.

Pyothorax-associated lymphoma: an unusual case with both T- and B-cell genotypes

Pyothorax-associated lymphoma (PAL) is a B-cell lymphoma which develops in the pleural cavity of patients with an over-20-year history of pyothorax. Aberrant expression of surface antigens is occasional in PAL, although genotype is not fully investigated. We report here a PAL with dual genotype, i.e., simultaneous immunoglobin (Ig) and T-cell receptor (TcR) gene rearrangement. An 82-year-old woman with pain on the left side of the chest was admitted. She had been suffering from pyothorax after artificial pneumothorax for treatment of tuberculosis of the pulmonary when she was 18 years old. The mass that was confined to the left pleural cavity affected by pyothorax was biopsied and histologically diagnosed as diffuse large cell lymphoma. The tumor cells were positive for CD20, CD16, and TIA-1 but negative for CD79a, CD45RO, CD43, CD3, and CD56. Surface antigen expression was further investigated in cultured cells, showing that the cultured cells did not express representative B-cell markers, except for CD20, as well as T-cell markers, but were positive for CD16, CD30, and CD103. Southern blotting revealed the monoclonally rearranged bands of both Ig heavy chain and TcR gene. The patients died of tumors 14 months after admission. Aberrant genotype and immunophenotype of PAL cells is discussed in reviewing the pertinent literature.

Establishment and characterization of unique cell lines derived from pyothorax-associated lymphoma which develops in long-standing pyothorax and is strongly associated with Epstein-Barr virus infection.

Malignant lymphoma frequently develops in the pleural cavity of patients with over 20 years' history of pyothorax. The term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. We established four novel lymphoma cell lines (OPL-3, -4, -5, and -7) from four patients with PAL. Characteristics of the four cell lines are as follows: B-cell nature with defective expression of B-cell and T-cell surface antigens, monoclonal pattern of Epstein-Barr virus (EBV) infection in lymphoma cells (thus indicating an etiological role of EBV for lymphomagenesis), complicated chromosomal abnormalities with numerous structural and numerical abnormalities, and occasional but distinct genome instability. These abnormalities in cell character might be caused by the specific circumstances of PAL lymphomagenesis, i.e., chronic inflammation. Thus, PAL cell lines could be useful in analysis of molecular mechanisms leading to malignancy in chronic inflammation.

Pyothorax-associated lymphoma: a review of 106 cases.

Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma developing in the pleural cavity after a long-standing history of pyothorax. Full details of PAL are provided here. Clinical and pathologic findings were reviewed in 106 patients with PAL collected through a nationwide survey in Japan. Age of the patients with PAL was 46 to 82 years (median, 64 years), with a male/female ratio of 12.3:1. All patients had a 20- to 64-year (median, 37-year) history of pyothorax resulting from artificial pneumothorax for treatment of pulmonary tuberculosis (80%) or tuberculous pleuritis (17%). The most common symptoms on admission were chest and/or back pain (57%) and fever (43%). Laboratory data showed that the serum neuron-specific enolase level was occasionally elevated (3.55 to 168.7 ng/mL; median, 18.65 ng/mL), suggesting a possible diagnosis of small-cell lung cancer. Histologically, PAL usually showed a diffuse proliferation of large cells of B-cell type (88%). In situ hybridization study showed that PAL in 70% of the patients was Epstein-Barr virus (EBV)-positive. PAL was responsive to chemotherapy, but the overall prognosis was poor, with a 5-year survival of 21.6%. This study established the distinct nature of PAL as a disease entity. PAL is a non-Hodgkin's lymphoma of exclusively B-cell phenotype in the pleural cavity of patients with long-standing history of pyothorax, and is strongly associated with EBV infection. Development of PAL is closely related to antecedent chronic inflammatory condition; therefore, PAL should be defined as malignant lymphoma developing in chronic inflammation.

Epstein-Barr virus (EBV)-positive pyothorax-associated lymphoma (PAL): chromosomal integration of EBV in a novel CD2-positive PAL B-cell line.

Pyothorax-associated lymphoma (PAL) is a clinico-pathological entity arising in the pleural cavity of patients with long-standing inflammatory pyothorax. PAL is closely associated with Epstein-Barr virus (EBV), but how this virus contributes to the development of the lymphoma is unknown. We have successfully obtained a novel EBV-infected PAL cell line, designated Pal-1. The cell line and its source coexpressed CD2 and CD20 molecules, but other representative B- and T-cell markers such as CD1, CD3, CD5, CD7, CD10 and CD19 were not found. The B-cell origin of Pal-1 cells was proven by rearrangement of the immunoglobulin heavy- and light-chain genes without rearranged T-cell receptor genes. Both the cell line and primary tumour cells carried monoclonal EBV genome. Although EBV genome is known to be maintained as circular extrachromosomal DNA, neither circular nor linear extrachromosomal EBV DNA was detectable in Pal-1 cells by in situ lysis gel analysis. Fluorescence in situ hybridization demonstrated viral integration at a marker chromosome mostly consisting of the centromere region of chromosome 1. The viral integration event may enhance a chromosomal instability at the insertion site. This cell line represents the first example of EBV integration in PAL and could enable the study of the potential role of integrated viral infection in the development of PAL as well as mechanism of the aberrant phenotype expression.

Enhanced Expression of Neuron‐specific Enolase (NSE) in Pyothorax‐associated Lymphoma (PAL)

Pyothorax‐associated lymphoma (PAL) is a B‐cell lymphoma of mostly large cell type developing in the pleural cavity of patients with long‐standing pyothorax. Neuron‐specific enolase (NSE) is an enolase comprising γ subunit and is located at high levels in neuronal and neuroendocrine cells, together with their neoplasias. Expression of NSE at protein and mRNA levels was examined in PAL and other types (non‐PAL) of non‐Hodgkin's lymphomas. In PAL, serum levels of NSE were elevated (5.32 to 168.0, mean 42.6 ng/ml) and tended to decrease after incisional biopsy followed by chemotherapy (2.38 to 195.5, mean 34.1 ng/ml). Two cell lines established from two cases of PAL produced and secreted NSE in the culture medium. Immunohistochemistry revealed that the positive rate for NSE staining in PAL (10 of 14 cases, 71.4%) was significantly higher than that in non‐PAL cases (6 of 38 cases, 15.8%) (P<0.01). RT‐PCR analysis showed that the expression levels of NSE mRNA in two cell lines and a biopsy sample from PAL were rather similar to those of the control samples from non‐neoplastic lymph nodes. These findings suggest the posttranscriptional regulation of NSE in PAL. Thus, an elevation of serum NSE level in patients with chronic pyothorax may be an indicator of PAL development.

Prognostic value of CD4+ lymphocytes in pleural cavity of patients with non-small cell lung cancer

BACKGROUNDFor patients with non-small cell lung cancer the TNM staging system and other conventional prognostic factors fail to predict accurately the outcome of treatment and survival. This study attempts to...

Prognostic value of CD4+ lymphocytes in pleural cavity of patients with non-small cell lung cancer

BACKGROUNDFor patients with non-small cell lung cancer the TNM staging system and other conventional prognostic factors fail to predict accurately the outcome of treatment and survival. This study attempts to determine the prognostic value for survival of the proportions of CD4+ lymphocytes in the pleural cavity (PLY) of patients with resectable non-small cell lung cancer.METHODSLymphocytes in the pleural cavity separated from 51 patients with non-small cell lung cancer were examined by flow cytometry to measure the proportions of CD4+ PLY. Univariate and multivariate analyses were performed to assess the association between the proportion of CD4+ PLY and survival.RESULTSThe 5 year survival rate of patients with percentage CD4+ PLY of ⩽30% was 84% whereas that of patients with %CD4+ PLY &gt;30% was 26.9%. The difference in survival between the %CD4+ PLY ⩽30% and %CD4+ PLY &gt;30% groups was significant (p&lt;0.0001). The %CD4+ PLY in those who survived for 5 years was significantly lower than that in the patients who died within 5 years (p&lt;0.0001). The difference in survival between patients with stage IA and IB lung cancer with %CD4+ PLY ⩽30% and those with %CD4+ PLY &gt;30% was also significant (p =0.015). Multivariate analysis showed that the proportion of CD4+ PLY (hazard ratio=6.9, 95% CI 0.045 to 0.47) and nodal status (hazard ratio=22.7, 95% CI 0.006 to 1.806) are significant and independent prognostic factors for the survival of patients with lung cancer.CONCLUSIONSThe proportion of CD4+ PLY may help to select patients who are likely to have a poorer prognosis after surgery and therefore may be suitable for consideration of adjuvant treatments. These results need confirmation in a larger prospective study.

Mechanism for the development of pyothorax-associated lymphoma.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PAL are of the type diffuse lymphoma of B cell and contain Epstein-Barr virus (EBV) DNA. This article reviews the mechanism for the development of PAL. The possible contribution of EBV infection, inflammatory cytokines and other genetic lesions, including the p53 gene, towards the growth advantage of neoplastic cells is described. Although the presence of EBV is focused in PAL cells, the contribution of EBV-mediated growth promotion in PAL is limited. Another important characteristic of PAL is that the virus antigen-positive lymphoma develops in patients with pyothorax, in whom the systemic immunodeficiency is unlikely to be present. Therefore, in the course of the development of PAL, the mechanism for the evading host immune surveillance must be obvious. In this context, the production of an immunosuppressive cytokine from PAL cells, human histocompatibility leukocyte antigen class I alleles of patients with PAL, and the mutations of cytotoxic T lymphocyte epitopes in an EBV-latent antigen are described. These mechanisms could be involved in the development of PAL, an EBV-positive lymphoma developing in an immunocompetent host, and also shed light on the tumorigenesis of other EBV-positive neoplasms and on the lymphomagenesis of other inflammatory lesions.

Expression of Epstein-Barr virus latent infection genes and oncogenes in lymphoma cell lines derived from pyothorax-associated lymphoma.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. The term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of the B-cell type and contain Epstein-Barr virus (EBV) DNA. We have established 2 lymphoma cell lines from biopsy specimens of PAL cases, OPL-1 and OPL-2, and examined their growth characteristics and the expression of EBV latent infection genes and oncogenes. OPL-2 exhibited a more rapid growth and higher saturation density than OPL-1, and only OPL-2 exhibited colony-forming activity in soft agar. OPL-1 and -2 were positive for B-cell differentiation markers and showed clonal surface immunoglobulins. Both line contained a single predominant form of episomal EBV DNA, indicating clonal cellular proliferation of an EBV-infected progenitor cell. OPL-1 and -2 contained type B and A EBV genome, respectively. Expression of EBV nuclear antigen (EBNA)2 mRNA and protein was detected by Northern and Western blot analysis in OPL-1, but not in OPL-2. On the other hand, the expression of latent membrane protein (LMP)1 mRNA in both OPL-1 and -2 was extremely weak and detectable only by reverse transcription-polymerase chain reaction. Protein expression of LMP1 was not observed by Western blot analysis or immunocytochemistry. Both lines expressed c-myc mRNA. Only OPL-1 expressed mRNA of c-fgr, an oncogene whose expression is upregulated by EBNA2. Both OPLs expressed bcl-2 mRNA without detectable expression of LMP1 protein.

Induction of inflammatory cytokines in the pleural effusion of cancer patients after the administration of an immunomodulator, Ok-432: Role of IL-8 for neutrophil infiltration

When OK-432, a well-known streptococcal preparation for an anti-tumour drug, was administered into the pleural cavity of patients with malignant pleurisy, a rapid and prominent leukocytosis, predominantly consisting of neutrophils, was observed in the cavity. Neutrophil infiltration usually peaked 6-9 h after OK-432 administration, and levelled down after 24 h. Prior to the neutrophil accumulation, transient but marked elevation of various inflammatory cytokine levels including IL-1 beta, TNF-alpha, IL-8 and G-CSF was observed. In particular, IL-8 levels increased more than 10-fold, while GM-CSF did not change significantly. A good correlation between IL-8 levels and neutrophil chemotactic response was observed particularly during 0-3 h. Specific neutralization or removal of IL-8 by antibody column abrogated half of the neutrophil chemotaxis, while neutralization of C5a removed around 40%. Sequential removal of IL-8 and C5a abrogated totally 80% of chemotaxis, confirming that these two factors are mostly responsible for the neutrophil chemotaxis in the pleural fluids. These results have suggested that rapid neutrophil infiltration induced by OK-432 in vivo is ascribable largely to IL-8 and in part to C5a.

Interleukin-8: an important neutrophil chemotaxin in some cases of exudative pleural effusions.

It was hypothesized that IL-8, a neutrophil chemotaxin, contributes to the influx of neutrophils into the pleural cavity of patients with pleural effusions. Pleural fluids were collected from 57 patients including 13 with effusions due to congestive heart failure, 28 with pleural involvement by carcinoma, 5 with empyema, 4 with parapneumonic effusions complicating bacterial pneumonia, 3 with hemothorax, 3 with tuberculosis, and 1 with rheumatoid arthritis. All exudate groups had significantly higher IL-8 concentrations than the CHF group (p < .001). In 18 of the exudate fluids, the concentrations of IL-8 was equal to or in excess of the optimal concentration of IL-8 which causes neutrophil chemotaxis in vitro. Between 20 and 90% of the chemotactic activity in the fluids was removed by absorbing the IL-8 with an IL-8 affinity column. These data showed that IL-8 is a major chemotaxin in the fluid. The percentage of neutrophils in the fluids was not correlated with the IL-8 concentration. Although TNF alpha, a potent stimulator of IL-8 production, is present in some pleural effusions, no correlation was found between the concentrations of IL-8 and TNF alpha in the fluids. The data suggest that IL-8 contributes to the neutrophil influx into the pleural space of patients with pleural exudates in conjunction with other chemoattractants. It is unlikely that TNF alpha is the sole stimulus for the IL-8 production in pleural disease states.

Eosinophil Colony-stimulating Factor Induced by Administration of Interleukin-2 into the Pleural Cavity of Patients with Malignant Pleurisy

Systemic administration of interleukin (IL)-2 to patients with malignant diseases induces peripheral eosinophilia. In the present study, to clarify the mechanism of eosinophilia induced by IL-2, we examined the changes in the number of eosinophils and eosinophil colony-stimulating factor (Eo-CSF) activity in the pleural fluids of six patients with malignant pleurisy caused by lung cancer or malignant mesothelioma during and after intrapleural administration of IL-2. Results showed that intrapleural administration of IL-2 induced marked eosinophilia in the pleural fluid and moderate eosinophilia in the peripheral blood, and that during IL-2 administration, marked Eo-CSF activity appeared in the pleural fluid before increase in the number of eosinophils, but that this activity did not appear in the peripheral blood. This Eo-CSF activity was inhibited by a combination of anti-IL-5 antibody, anti-IL-3 antibody, and anti-granulocyte/macrophage colony-stimulating factor (anti-GM-CSF) antibody, but not by each antibody alone. Chemotactic activity for eosinophils was also detected in the pleural fluid during IL-2 treatment. These results suggest that eosinophilia in the pleural fluid induced by IL-2 injection into the pleural cavity of patients with malignant pleurisy is due to the Eo-CSF activities of various components, including IL-5, IL-3, and GM-CSF, and chemotactic factors for eosinophils induced locally in the pleural cavity by IL-2.