Hypotension and acute pulmonary insufficiency following transfusion of autologous red blood cells during surgery: a case report and review of the literature.

Transfusion of autologous blood is associated with fewer complications, although all untoward events of transfusion may not be negated with this strategy. We report a case of acute pulmonary insufficiency and hypotension following transfusion of autologous packed red blood cells (PRBCs) in a patient, who was undergoing major surgery. Anti-HLA class-I and class-II and anti-granulocyte antibodies were measured in the unit and in the recipient. Neutrophil (PMN)-priming activity was measured as the augmentation of the formyl-Met-Leu-Phe-activated respiratory burst. No immunoglobulins were identified; however, significant lipid-priming activity was present in the implicated, autologous PRBC unit that primed PMNs from both healthy people and the recipient. In addition, lipids, identical to those that accumulate during PRBC storage, caused significant hypotension when infused into rats at similar concentrations found in stored PRBCs. We conclude that the observed transfusion-related acute lung injury reaction with significant hypotension may be the result of two independent events: the first is related to inherent host factors, in this case major surgery, and the second is the infusion of lipids that accumulate during the routine storage of PRBCs.

[Diagnostic imaging of "body packers"].

Drug smuggling by intra-abdominal concealment, so called "body packing," has recently increased, even in Japan. Because of fatal drug intoxication and other adverse side effects, it is important to make a radiological diagnosis of body packers as soon as possible. A retrospective analysis of the images of plain abdominal radiography, computed tomography (CT) and ultrasound (US) was performed in twenty-three body packers to evaluate the imaging characteristics of three drugs (cannabis, cocaine and heroin). Cannabis (16 patients) and cocaine (5 patients) packages were demonstrated as well-demarcated rectangular-shaped high-density shadows surrounded by gas halo ("double condom sign") in abdominal plain radiographs and CT. Heroin packages (2 patients) were demonstrated as obscure shadows and were difficult to identify on plain radiographs, because they resembled stool masses. US was performed in one cannabis patient because of the refusal of radiological examination, and packages were demonstrated as round echogenic structures with dorsal echo extinctions. In conclusion, abdominal plain radiography, CT and US represent valuable diagnostic modalities in the assessment of body packers.

High sensitivity to peripheral blood lymphocytes and low HLA-class I antigen expression of small cell lung cancer cell lines with diverse chemo-radiosensitivity.

Three cell lines of small cell lung cancer (SCLC), which were established from specimens of untreated primary tumors biopsied by diagnostic bronchofiberscopy, were analyzed for immunological characteristics. These cell lines showed considerable heterogeneity in chemo-radiosensitivity, which was well correlated with clinical responses of the respective tumors, but their HLA-class I antigen expressions were equally depressed and they were susceptible to peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells, irrespective of their diverse chemo-radiosensitivity. Treatment of the cell lines with recombinant immune interferon (rIFN-gamma) increased their HLA-class I antigen expression and conversely depressed PBL sensitivity but not LAK sensitivity. This inverse relationship between HLA-class I expression and PBL susceptibility was also demonstrated using other pairs of autologous PBL and SCLC cell lines. rIFN-gamma changed neither HLA-class II antigen nor SCLC-specific antigen expression under the same experimental conditions. In vitro immunization of allogeneic peripheral blood lymphocytes with rIFN-gamma-treated SCLC cells induced allo-specific killer cells which lysed rIFN-gamma-treated more strongly than non-treated SCLC cells. These results suggest that reduced HLA-class I antigen expression of SCLC could protect the cancer from attack of killer T cells in spite of the higher sensitivity to PBL or LAK cells.

Generation of a small cell lung cancer variant resistant to lymphokine-activated killer (LAK) cells: association with resistance to a LAK cell-derived, cytostatic factor.

Cells of OS2-RA, a human small cell lung cancer line sensitive to lymphokine-activated killer (LAK) cells, were repeatedly cocultured with human LAK cells. Fourteen cycles of the coculture produced a variant, termed OS2-RA-R, capable of growing successfully in the presence of LAK cells. OS2-RA-R showed a moderate resistance to lysis by LAK cells in 4-h 51Cr release assays. OS2-RA-R acted positively as a cold target for lysis of OS2-RA by LAK cells, suggesting no loss of the binding site for LAK cells on the cell surface of the variant. On the other hand, LAK cells were shown to produce a factor capable of suppressing the proliferation of OS2-RA and certain other cell lines but not lymphocytes. Interestingly, OS2-RA-R exhibited a substantial resistance to the cytostatic activity of LAK cell supernatants. The cytostatic factor, eluted at the 57-kDa fraction in gel filtration, showed no activity of interleukin 1, gamma-interferon, transforming growth factor beta, or tumor necrosis factor. These results suggest that LAK cells exhibit antitumor activity through not only rapid cytolysis but also slow-acting cytokine production, and the successful growth of OS2-RA-R in a coculture with LAK cells is the result of acquiring resistance to these two different LAK cell phenomena.

Acquired T cell specific deficiency other than acquired immunodeficiency syndrome (AIDS).

Evidence of an acquired T cell-specific deficiency distinct from acquired immunodeficiency syndrome (AIDS) in a 63-yr-old Japanese female is provided. Recently, this patients suffered from primary invasive pulmonary aspergillosis. Skin tests to purified protein derivative of tuberculin (PPD) and Aspergillus antigens were negative. Upon admission to our hospital, her lymphocytes were exclusively unresponsive to T cell mitogens (concanavalin A, phytohemagglutinin, and OKT 3). The level of cells defined by monoclonal antibodies (CD1, CD2, CD3, CD4, WT31, and CD5) was less than 3%. In contrast, no decrease in the number of red blood cells, platelets, neutrophils or B cells was apparent. Five years ago, the patient had a normal white blood cell and lymphocyte count. However, over the following 4 yr, she developed lymphopenia. With medication, her pulmonary disease recovered, while lymphopenia still continued. The levels of immunoglobulins, complements and enzyme activities (adenosine deaminase and purine nucleoside phosphorylase) were normal. Moreover, several tests for HIV (ELISA and Western bolt) were negative suggesting that the T cell-specific deficiency was not a congenital immunodeficiency or AIDS but rather a new type of acquired immunodeficiency.

A comparative trial of LC9018 plus doxorubicin and doxorubicin alone for the treatment of malignant pleural effusion secondary to lung cancer.

The efficacy and safety of intrapleural LC9018 (Yakult Co. Ltd., Tokyo, Japan) with or without doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) were evaluated in a randomized, controlled trial performed in 95 patients with malignant pleural effusions secondary to lung cancer. Seventy-six patients were eligible for the assessment of efficacy. The response rate for treatment with intrapleural doxorubicin plus LC9018 (38 patients) was 73.7%, which was significantly higher than the response rate of 39.5% for the control group treated with doxorubicin alone (38 patients) (P less than 0.01). The LC9018 group also showed a significantly greater improvement in performance status (PS) and symptoms (chest pain, chest discomfort, and anorexia) than the control group (P less than 0.05). A significant prolongation of survival was noticed in the LC9018 group (P less than 0.05). The main side effects of LC9018 were fever and transient hepatic dysfunction, but there were no serious adverse reactions. These results suggest that the intrapleural instillation of LC9018 can be recommended for the treatment of malignant pleural effusions.

Characterization and purification of an immunosuppressive factor produced by a small cell lung cancer cell line.

The present study was undertaken to determine whether small cell lung cancer (SCLC) cell lines produce immunosuppressive factors and, if they do, to characterize the factors. The supernatants of SCLC cell lines, H69 and N857, inhibited not only the blastogenic response of human peripheral blood lymphocytes (PBL) to phytohemagglutinin or concanavalin A, but also the cytotoxic activity of lymphokine-activated killer cells. Neither was inhibited by supernatants from non-SCLC cell lines PC9, QG56, and A549. The immunosuppressive activity of H69 supernatant was stable upon heating to 56 degrees C for 60 min, but labile when heated to 70 degrees C for 10 min. The activity was abolished after dialysis at pH 2.0 or pH 11.0, but not at pH 4.5 or pH 9.0. Digestion with trypsin or proteinase eliminated the immunosuppressive activity, whereas treatment with neuraminidase, mixed glycosidase, DNase or RNase had no effect, suggesting that the immunosuppressive activity in H69 supernatant is due to a protein factor. This H69-derived immunosuppressive factor was isolated by ion exchange chromatography using a gradient of 0.04 to 0.08 M NaCl solution. Gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the factor to have molecular weights of 98 kD and 102 kD, respectively. These results suggest that SCLC cells produce a potent immunosuppressive factor which may account for the immune deficiency in SCLC patients.

Chemo-radioresistance of small cell lung cancer cell lines derived from untreated primary tumors obtained by diagnostic bronchofiberscopy.

New cell lines of small cell lung cancer (SCLC) were established from specimens of untreated primary tumors biopsied by diagnostic bronchofiberscopy. The advantage of this method was ease of obtaining specimens from lung tumors. Establishment of cell lines was successful with 4 of 13 specimens (30%). Clinical responses of the tumors showed considerable variation, but were well correlated with the in vitro sensitivity of the respective cell lines to chemotherapeutic drugs and irradiation. One of the cell lines was resistant to all drugs tested and irradiation, while another was sensitive to all of them. Although the acquired resistance of SCLC is the biggest problem in treatment, the natural resistance to therapy is another significant problem. Either acquired or natural, resistance mechanisms of SCLC may be elucidated by the use of such cell lines derived from untreated tumors. This method and these SCLC cell lines are expected to be useful for the serial study of biologic and genetic changes of untreated and pre-treated tumors, or primary and secondary tumors.

Human pulmonary infection with Corynebacterium equi.

A 28 year old man with no underlying disease developed a cavity and multiple nodules in the lung from which Corynebacterium equi was isolated. He experimented with organic solvents and microorganisms including Corynebacterium species for several years. Computed tomography of his pulmonary lesions revealed that these nodules were related to the bronchial tree. Histologically, the lesions were compatible with nonspecific inflammatory changes. The clinician must suspect the pulmonary infections with Corynebacterium species even if the patient has no underlying disease.

Synergy of Nocardia rubra cell wall skeleton and interleukin 2 in the in vivo induction of murine lymphokine-activated killer cell activity.

Combination of an ip injection of Nocardia rubra cell wall skeleton (N-CWS) and 3 daily sc injections of human recombinant interleukin 2 (rIL 2) into C3H/HeN mice resulted not only in a significant increase in the number of peritoneal cells (PC) but also in a potent induction of their lymphokine-activated killer (LAK) activity, compared with results obtained with N-CWS or rIL 2 alone. The augmented LAK activity of PC was mediated by nonadherent, nonphagocytic, Thy-1.2+(-)- and asialo GM1+ cells. Nonadherent PC induced by an ip injection of N-CWS bound more 125I-labeled rIL 2 than did normal, nonadherent PC, and generated high LAK activity when cultured overnight with rIL 2. In contrast, normal, nonadherent PC responded only weakly to the overnight stimulation with rIL 2. The phenotype of N-CWS-induced PC with an elevated IL 2 responsiveness was Thy-1.2+(-)-, Lyt-1.1-, Lyt-2.1- and asialo GM1+, suggesting that the N-CWS-stimulated LAK precursors were derived mainly from the NK cell lineage. However, mature T cells may also be involved in this mechanism, because N-CWS failed to augment the IL 2 responsiveness of nonadherent PC in BALB/c nu/nu mice. Treatment of C57BL/6N mice bearing solid Lewis lung carcinoma (3LL) tumors with an intratumoral injection of N-CWS followed by 6 daily sc injections of rIL 2 resulted in the apparent suppression of tumor growth, while N-CWS or rIL 2 alone produced no such suppression. These results suggest that N-CWS augments the antitumor effect of rIL 2 by accumulating LAK precursors and elevating their responsiveness to rIL 2 at the injection site.

Augmentation of murine lymphokine-activated killer cell induction by a factor produced by Nocardia rubra cell wall skeleton-stimulated T cells.

Four-hour exposure of C3H/HeN mouse spleen cells to Nocardia rubra cell wall skeleton (N-CWS) before 4-day culture with a suboptimal dose of human recombinant interleukin 2 (rIL 2) augmented the induction of lymphokine-activated killer (LAK) cell activity, whereas the treatment with N-CWS alone induced no cytotoxicity. In accordance with this, the IL 2 binding activity of spleen cells was augmented by combined stimulation with N-CWS and rIL 2. The augmented cytotoxicity was mediated by Thy-1.2+, Lyt-1.1-, Lyt-2.1- and asialo GM1+ cells. Cell cultures in diffusion chambers revealed that N-CWS-treated spleen cells produced a LAK cell induction-helper factor (LAK-helper factor, LHF) when cultured with rIL 2. The LHF production required Thy-1.2+, Lyt-1.1+, Lyt-2.1+ and asialo GM1- cells, and the coexistence of unstimulated accessory cells was also essential for the LHF production. Cells responding to both LHF and rIL 2 to generate LAK activity were Thy-1.2-, Lyt-1.1-, Lyt-2.1- and asialo GM1+. The culture fluid of spleen cells stimulated with both N-CWS and rIL 2 contained no tumor necrosis factor (TNF) activity, and the additional stimulation with N-CWS caused no production of either IL 2 or interferon (IFN). Murine recombinant interleukin 1 alpha (Mu-rIL 1 alpha) could not replace the augmentative effect of N-CWS on LAK cell induction. These results suggest that in the presence of rIL 2, N-CWS stimulates murine T cells to produce LHF that is probably distinct from IL 1, IL 2, TNF and IFN.

Enhanced tumor growth and metastatic spread of an MH134 variant lacking a part of the MM antigen: a possible role of antibody-dependent cellular cytotoxicity in control of tumor growth and metastases.

The role of antibody-dependent cellular cytotoxicity (ADCC) in host defense against tumor growth and metastasis was investigated with MH134, an MM antigen-positive murine hepatoma, and MH134-M, a variant with enhanced tumorigenesis and metastasis, in syngeneic C3H/HeN mice. When inoculated subcutaneously into C3H/HeN mice, MH134-M tumors grew more rapidly than did MH134 tumors and consistently metastasized to the draining lymph nodes, whereas MH134 tumors did not. Also, MH134-M exhibited a significantly greater lung colonization potential than did MH134, when inoculated intravenously into C3H/HeN mice. In BALB/c nu/nu mice, however, solid MH134 tumors grew and metastasized to the same extent as MH134-M, indicating that there is no significant intrinsic difference between these two tumor lines in proliferative or metastatic capacity. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting, performed after SDS-PAGE analysis of cellular extracts with a monoclonal antibody (MAb) that recognizes a part of the MM-antigen, revealed that the cells of MH134-M lack at least a part of the MM antigen. Sera of C3H/HeN mice bearing solid MH134 tumors were found to contain anti-MM-antigen antibodies, when tested by immunoblotting of SDS-PAGE-developed materials. Cytotoxicity testing in which thioglycollate-induced peritoneal macrophages were used as effector cells revealed that antibodies present in sera strongly induced ADCC to MH134 but not to MH134-M. On the other hand, sera of MH134-M tumor-bearing C3H/HeN mice neither contained anti-MM-antigen antibodies nor induced ADCC to MH134 or MH134-M tumor cells. Intravenous injection of carrageenan into C3H/HeN mice bearing solid MH134 tumors significantly enhanced tumor growth, whereas the growth of subcutaneously injected MH134-M tumors was not influenced by this treatment. These results suggest that the enhanced tumorigenesis and metastasis of the MH134-M line in C3H/HeN mice are based, at least in part, on significant loss of the MM antigen and the resultant inability to induce ADCC-triggering antibody production during tumor growth.

Augmentative effect of Nocardia rubra cell-wall skeleton on the induction of human lymphokine-activated killer (LAK) cells by the production of LAK cell helper factor(s).

Nocardia rubra cell wall skeleton (N-CWS) was found to synergistically augment lymphokine-activated killer (LAK) cell generation from human peripheral blood mononuclear cells (PBMC) in the presence of a suboptimal dose of recombinant interleukin-2 (rIL-2). N-CWS increased the number of PBMC expressing IL-2 receptor on their surfaces, and the presence of N-CWS at the early stage of the culture period was essential for the exertion of its augmentative activity on the LAK induction. The predominant phenotype of LAK precursor cells responding to N-CWS and rIL-2 was CD3- CD16+. Culture supernatant from N-CWS-stimulated PBMC was found to act as a substitute for N-CWS in the induction of LAK generation in the presence of rIL-2, suggesting that these cells produced a factor capable of augmenting LAK cell induction (LAK helper factor, LHF). LHF was found to have a molecular mass of 29 kDa by gel filtration, and could also function as a killer helper factor to augment allo-antigen-specific cytotoxic T lymphocyte generation from human peripheral blood T cells as well as murine thymocytes. LHF showed no species specificity, indicating that it is different from IL-4. The enhancing activity of LHF was not neutralized with anti-TNF alpha, anti-IL-1 alpha, or anti-IL-1 beta antibodies. Furthermore, no tumor necrosis factor-alpha (TNF alpha), TNF beta, IL-1 alpha, beta, IL-2, IL-5, IL-6 or interferon activity was detected in semi-purified LHF during enzyme-linked immunosorbant assay and biological assays. The present findings indicate that LHF produced from N-CWS-stimulated PBMC is a molecule distinct from TNF alpha, TNF beta, interferon, IL-1, -2, -4, -5, and -6, and suggest that LHF might be a novel lymphokine involved in LAK generation.

Induction of tumoricidal macrophages from bone marrow cells of normal mice or mice bearing a colony-stimulating-factor-producing tumor.

Nonadherent cells of the bone marrow of C3H/HeN mice were incubated for 3 days with the culture supernatant of an L-929 cell line containing macrophage-colony-stimulating factor. Approximately, 70% of the cells became phagocytic, adherent to plastic dishes and positive for nonspecific esterase staining. The adherent cells exhibited a weak tumoricidal activity against syngeneic mammary carcinoma cells, and the cytotoxicity was strongly augmented by the addition of bacterial lipopolysaccharide to the cytotoxicity assay. The cytotoxicity induced by lipopolysaccharide was also shown to be mediated by Thy1.2- and asialo-GM1+ cells, and was abrogated by the addition of carrageenan. Macrophage-colony-stimulating-factor-producing (D66) and nonproducing (A23) variants were separated from the MM48 tumor line in in vitro culture following limiting dilution. There was no difference between these two variants in either the in vitro growth rate or the susceptibility to macrophage-mediated cytotoxicity. C3H/HeN mice inoculated i.p. with D66 survived longer than did those inoculated i.p. with A23. C3H/HeN mice bearing D66 or A23 as an ascitic form were given i.p. injections of Nocardia rubra cell wall skeleton (N-CWS). N-CWS significantly prolonged the survival period of mice bearing D66, whereas it exhibited no apparent antitumor effect on mice bearing A23. The increase in the cell number of D66 in the peritoneal cavity was significantly retarded, compared with that of A23. In contrast, the number of peritoneal macrophages increased more in D66-bearing mice than in A23-bearing mice. The increase in the peritoneal macrophage number was further augmented by an i.p. injection of N-CWS. Peritoneal macrophages of D66-bearing mice exhibited apparent tumoricidal activity against MM48 tumor cells in the presence of lipopolysaccharide, and the cytotoxicity was significantly augmented by i.p. injection of N-CWS. On the other hand, the responsiveness of peritoneal macrophages to lipopolysaccharide was found to be poor in A23-bearing mice and the tumoricidal activity was only weakly augmented by N-CWS. These results strongly suggest that M-CSF plays an important role not only in the maturation of macrophage progenitors but also in the induction and the accumulation of activated macrophages.

Combined therapy of mice bearing a lymphokine-activated killer-resistant tumor with recombinant interleukin 2 and an antitumor monoclonal antibody capable of inducing antibody-dependent cellular cytotoxicity.

The ability of lymphokine-activated killer (LAK) cells to mediate antibody-dependent cellular cytotoxicity and its efficacy against a LAK-resistant tumor were investigated. Cells of the MH134 murine hepatoma line are scarcely lysed by LAK cells generated in vitro by incubation of C3H/HeN mouse spleen cells with human recombinant interleukin 2 (rIL 2). However, the splenic LAK cells potently lysed the LAK-resistant tumor cells in the presence of 11G2, a monoclonal antibody (MAb) of the IgG1 isotype reactive with a part of MM antigen. Peritoneal cells induced by daily i.p. injections of rIL 2 not only exhibited LAK activity but also mediated antibody-dependent cellular cytotoxicity against MH134 tumor cells in the presence of 11G2. The peritoneal cells exhibiting these cytotoxic activities were found to be nonadherent and nonphagocytic mononuclear cells possessing a similar cell surface phenotype as that of splenic LAK cells, that is Thy-1.2+ approximately -, Lyt-1.1-, Lyt-2.1-, and asialo GM1+. Treatment of spleen cells with antibodies and complement before culture with rIL 2 revealed that the phenotype of splenic LAK precursors is Thy-1.2- and asialo GM1+. The in vivo induction of peritoneal LAK cells in response to i.p. injections of rIL 2 was markedly depressed in C57BL/6 beige mice but was normally accomplished in BALB/c nude mice. Combined therapy of C3H/HeN mice bearing MH134 ascitic tumor with i.p. injection of rIL 2 and 11G2 brought about potent suppression of the tumor growth, resulting in the significant increase in the number of tumor-free mice, whereas neither rIL 2 nor the MAb could exhibit such a potent antitumor effect when used alone. Injection (i.v.) of anti-asialo GM1 antibody not only blocked the induction of peritoneal LAK cells by rIL 2 but also abrogated the development of the antitumor effect of the combined therapy. These results strongly suggest that combination of antitumor MAbs capable of inducing antibody-dependent cellular cytotoxicity with rIL 2 therapy could result in the generation of potent antitumor effects against LAK-resistant tumors and that asialo GM1-positive non-T-cell populations including cells of the natural killer cell lineage are essential, at least in part, for development of the antitumor effects of the combined therapy with rIL 2 and MAbs.

Augmentative effect of Nocardia rubra cell-wall skeleton (N-CWS) on lymphokine-activated killer (LAK) cell induction.

The present study elucidated that N-CWS augments the cytolytic activity against 3LL tumor cells of LAK cells from N-CWS-immunized mice administered i.p. with rIL-2. This augmentative effect of N-CWS was not seen when the LAK cells were prepared from normal mice. The cytolytic activity was predominantly expressed in the NAPC prepared from the site of injection of rIL-2, and repeated administrations of rIL-2 were required to induce and maintain this potent cytolytic activity in vivo. Serological analysis revealed that the LAK cells were positive for Thy 1.2 and asialo GM1 antigens and that they were not classical CTL or NK cells. The administration of rIL-2 statistically prolonged the MST of mice bearing LAK-sensitive 3LL cells but not the MST of mice bearing LAK-resistant EL-4 leukemia. Furthermore, combination therapy with N-CWS and rIL-2 prolonged the MST of the mice more than the therapy with rIL-2 alone. These results suggest that LAK cells potentiated with N-CWS would be useful for immunotherapy of malignant neoplasms.

Synergistic antitumor effects of BCG and monoclonal antibodies capable of inducing antibody-dependent cell-mediated cytotoxicity.

Three monoclonal antibodies (MAbs) of different immunoglobulin subclasses against MH134 murine ascitic hepatoma cells, detecting the same antigenic determinant of tumor-associated antigen of the tumor cells, were tested for their ability to produce a synergistic antitumor effect with Mycobacterium bovis BCG in C3H/HeN mice. 12A2 (IgG2a) induced both antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against the tumor cells. C3H/HeN mice were inoculated ip with MH134 tumor cells (day 0), and received an ip injection of BCG (day 1) and/or 12A2 (day 5). The combined therapy with BCG and 12A2 brought about a significant prolongation of the survival period, whereas either BCG or the MAb alone exhibited poor therapeutic effectiveness. 11G2 (IgG1), inducing ADCC but not CDC against MH134 tumor cells, was shown to exhibit antitumor effects as potent as those of 12A2, when used in combination with BCG. However, 7C2 (IgM), capable of inducing CDC but not ADCC to the tumor cells, produced no apparent synergistic effect with BCG. ADCC of BCG-induced peritoneal cells was mediated by the adherent cell population of the cells and abolished by the addition of carrageenan, suggesting that the effector cells of the cytotoxicity were macrophages. Moreover, carrageenan abolished the combined antitumor effect of BCG and these MAbs in the serological Winn assay. These results suggest that activated macrophages play a major role in the synergistic antitumor effect of BCG and MAbs capable of inducing ADCC against MH134 tumor.

Effect of Nocardia rubra cell wall skeleton on augmentation of cytotoxicity function in human pleural macrophages.

The ability of Nocardia rubra cell wall skeleton (N-CWS) to augment macrophage cytotoxicity function was examined using human pleural macrophages prepared from 32 malignant pleural effusions and 53 pleural washings. The cytostatic activity of pleural macrophages for human lung cancer cells (PC-9) was augmented following incubation of pleural mononuclear cells with 10 micrograms/ml N-CWS for 24 h. Macrophage activity was increased by direct interaction of macrophages with N-CWS or by incubation of macrophages with supernatant culture fluids from pleural lymphocytes with N-CWS. The cytotoxic potential of the pleural macrophages obtained from patients treated with 500 micrograms of N-CWS intrapleurally was also increased. The heat and acid stability studies revealed that the culture fluids from pleural lymphocytes treated with N-CWS contained macrophage activation factor in addition to interferon-gamma. These results suggest that direct and indirect macrophage activation is part of the mechanism in which N-CWS has a clinical effect on malignant pleural effusions.