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Biomedical subjects

J J Ellner

Publications and source records attributed to J J Ellner.

At least 163 records · Page 9Linked to original sources
PubMed1987

Spontaneous production of a suppressor factor by a human macrophage-like cell line U937. II. Suppression of antigen- and mitogen-induced blastogenesis, IL 2 production and IL 2 receptor expression in T lymphocytes.

U937, a human macrophage-like cell line, spontaneously produces a factor which inhibited blastogenic responses of human blood T lymphocytes stimulated with tuberculin-purified protein derivative (PPD) or phytohemagglutinin (PHA). We investigated the mechanism of suppressor action of the U937 factor. The U937 suppressor factor inhibited interleukin 2 (IL 2) production by human blood T lymphocytes stimulated with PPD or PHA. IL 1 did not overcome the inhibitory action of the U937 factor on PPD-induced IL 2 production by human blood T lymphocytes. The U937 factor also inhibited the production of IL 2 by a human leukemic cell line, JURKAT, stimulated with PHA. The U937 suppressor factor interfered with the expression of Tac antigen (IL 2 receptor) on PPD- or PHA-stimulated blood T lymphocytes. The inhibitory activity of the U937 factor on Tac expression was not affected by the addition of IL 2 or a crude lymphokine-containing T cell supernatant. Tac expression was more sensitive than IL 2 production to inhibition by U937-conditioned medium. The U937 suppressor factor was precipitable by 33 to 67% saturated ammonium sulfate and was inactivated at pH 2 or pH 11. Sephacryl S-200 Gel filtration analysis of U937 culture supernatants revealed that the inhibitory activities for blastogenesis, IL 2 production, and Tac expression co-purified in fractions with an apparent m.w. between 67,000 and 130,000. These data indicate that U937 spontaneously produces a macromolecular suppressive factor with major locus of action on the production of IL 2 and the expression of the IL 2 receptor.

Cell Line↗
PubMed1987

Lymphocytes of persons with the acquired immunodeficiency syndrome and related conditions express reactivity with the monoclonal antibody 4D12 reflective of in vivo lymphocyte activation.

We observed that lymphocytes obtained from healthy persons generally expressed infrequent reactivity with the monoclonal antibody 4D12, an antibody raised against a cell line infected by the human T-lymphotropic virus type I. As had been observed previously, persons bearing HLA-B5 cross-reactive antigens and certain other allotypes had frequent lymphocyte reactivity with 4D12. Lymphocytes obtained from persons infected by the human immunodeficiency virus were highly reactive with 4D12 as were lymphocytes obtained from persons with other viral or bacterial infections. Flow cytometric studies revealed greater 4D12 reactivity by larger lymphocytes, and in vitro studies demonstrated that lectin-stimulated lymphocytes acquired 4D12-reactive antigens. There was also a significant correlation between expression of 4D12-reactive antigens and the presence of the interleukin-2 receptor as recognized by the monoclonal antibody anti-Tac. Thus, the monoclonal antibody 4D12 recognizes a lymphocyte surface antigen frequently expressed among persons with various acute and chronic infections. This antigen is a marker of lymphocyte activation.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Failure of immunosuppressive mechanisms in human Schistosoma mansoni infection with hepatosplenomegaly.

The basis for development of hepatosplenic disease and attendant morbidity in Schistosoma mansoni-infected individuals is uncertain but may relate to defective modulation of immunopathology. Individuals 14 to 30 years of age from a village in the Nile Delta in Egypt were selected for study: 32 were infected with S. mansoni but lacked hepatosplenomegaly (mean fecal egg excretion +/- standard error of the mean, 1,142 +/- 79 eggs per g), 9 had S. mansoni infection and hepatosplenomegaly (1,267 +/- 197 eggs per g), and 12 were uninfected. The ratio of OKT4 helper/OKT8 suppressor cells in peripheral blood mononuclear cells was reduced in infected subjects without hepatosplenomegaly to 1.4 +/- 0.1 compared with a ratio of 1.7 +/- 0.1 (P less than 0.05) in uninfected subjects. In contrast, this ratio was increased in the group with hepatosplenomegaly to 2.7 +/- 0.3 (P less than 0.01). Schistosome antigen-induced [3H]thymidine incorporation in peripheral blood mononuclear cells was comparable in infected subjects without (5,837 +/- 1,009 cpm) and with (3,329 +/- 738 cpm; P greater than 0.1) hepatosplenomegaly. Depletion of adherent suppressor cells significantly increased the responses in the group lacking organomegaly (14,028 +/- 1,683 cpm; P less than 0.001) but not in the hepatosplenomegaly group (5,046 +/- 1,830 cpm; P greater than 0.5); this difference in response of nonadherent cells to soluble worm antigenic preparation was statistically significant (P less than 0.02) and not explained by quantitative shifts in OKT8 suppressor cells. Thus, in S. mansoni infection, subjects with hepatosplenomegaly are distinctive in their lack of an immunosuppressive balance of T-lymphocyte subpopulations and in the absence of functional adherent suppressor cells. Defective immunoregulatory mechanisms could be important in the genesis of hepatosplenic disease and its morbid sequelae.

Adolescent↗
PubMed1987

Spectrum of immunoregulatory functions and properties of human alveolar macrophages.

In health, pulmonary alveoli are maintained free of inflammatory responses to inhaled foreign antigens. The specific role of alveolar macrophages (AM) in modulating the local cellular immune response to antigens is controversial. Immunoregulatory function and properties of AM and blood monocytes (MN) were compared. The AM were obtained by bronchoalveolar lavage of healthy volunteers, MN by adherence of peripheral blood mononuclear cells to plastic. These accessory cells were added in increasing ratios to a responder population rendered rigorously accessory cell-dependent by nylon wool adherence and depletion of cells bearing the surface Class II MHC determinant, HLA-DR. At low ratios of mononuclear phagocytes to lymphocytes (less than or equal to 1:10), MN and AM supported significant and comparable blastogenic responses to tetanus toxoid (3H-thymidine incorporation at a 1:10 ratio was 9,697 +/- 2,508 for MN and 8,969 +/- 1,454 for AM, mean cpm +/- SE, n = 9, p = NS) and other antigens. Interleukin-1 (IL-1) activity in supernatants of MN stimulated with lipopolysaccharide (LPS), 10 micrograms/ml, was 115 +/- 28 versus 67 +/- 21 U/ml in supernatants of AM (n = 9, p greater than 0.2). At suboptimal concentrations of LPS, however, MN expressed more IL-1 activity than did AM. The specific mean fluorescence intensity of surface expression of HLA-DR determinants as assessed by flow cytometry was similar for MN and AM. At the higher ratio of 1:2, MN supported 32% increased responses to tetanus toxoid compared with that at 1:5 (p less than 0.05). In contrast, AM at a ratio of 1:2 suppressed lymphocyte response by 69% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Antigen responsiveness during tuberculosis: regulatory interactions of T cell subpopulations and adherent cells.

Previous studies from this laboratory demonstrated that adherent mononuclear cells selectively decreased in vitro tuberculin responses in some anergic patients with tuberculosis; subsequently this adherent suppressor cell was characterized as a monocyte. The current study of 41 patients with active pulmonary tuberculosis examined whether T cell subpopulations also acquired antigen-specific suppressor function during Mycobacterium tuberculosis infection, contributed to monocyte-mediated suppression of tuberculin responses, or both. Alteration in the numbers of circulating T-helper (Leu 3a) and T-suppressor (Leu 2a) cells was not observed in patients with tuberculosis, nor did Leu 2a cells selectively modulate in vitro tuberculin responses. The numbers of circulating T gamma cells, a subset of T cells identified by surface receptors for the Fc portion of IgG (Fc gamma R), was increased twofold in patients with active pulmonary tuberculosis. Depletion of T gamma cells from in vitro cell culture consistently and selectively increased tuberculin responsiveness of T cells from patients with tuberculosis. In addition, in the absence of T gamma cells, monocyte-mediated suppression of tuberculin responses was demonstrated in each patient observed. These studies demonstrate that during M. tuberculosis infection T gamma cells acquire antigen-specific suppressor cell activity and suggest that T gamma cells also contribution to immunoregulation modulating the expression of tuberculin-specific suppression by monocytes.

Adult↗
PubMed1987

Deleterious effect of ultraviolet-B radiation on accessory function of human blood adherent mononuclear cells.

The effects of ultraviolet-B radiation (UV-B) on accessory function of human blood adherent mononuclear cells (ADH) for antigen and mitogen-induced responses, and production by ADH of the amplifying cytokine interleukin 1 (IL-1) were examined. Responder lymphocytes were rendered accessory cell dependent by treatment of nonadherent cells with OKIal+complement. UV-B depressed accessory function of ADH in a dose-dependent manner. UV-B at 5 mJ/cm2 decreased accessory function of 2 x 10(4) ADH for tetanus toxoid-induced responses (measured as incorporation of 3H-thymidine) by 84% (P less than 0.001, n = 6) and phytohaemagglutinin-induced responses 91% (P less than 0.001, n = 4). UV-B also decreased accessory activity of peripheral blood mononuclear cells but not Epstein-Barr virus-transformed B cells for a PPD-reactive T cell line. Viability was approximately 90% 0-72 h after exposure of ADH to 5 mJ/cm2 of UV-B. Interleukin 1 (IL-1) activity of supernatants of ADH was assayed on C3H/HeJ mouse thymocytes. Pretreatment of ADH with 5 mJ/cm2 UV-B decreased lipopolysaccharide-stimulated IL-1 activity from 169 +/- 34 (mean U/ml +/- s.e.) to 4 +/- 1 (P less than 0.01, n = 4). Lysates of UV-B irradiated. LPS-stimulated ADH had no discernible IL-1 activity. Addition of IL-1 partially restored accessory activity of UV-B irradiated ADH for lymphocyte responses to TT. Exposure of ADH to TT or PHA for 30 min before irradiation blocked the inhibitory effect of UV-B on accessory activity. Thus, low doses of UV-B are deleterious to accessory function and to production of IL-1 by ADH. Interference with production of cytokines and with initial interactions of accessory cells with antigen and mitogen may be critical to the effects of UV-B on immunoregulatory function of ADH.

Antigen-Presenting Cells↗
PubMed1986

Defective interleukin 2 production and responsiveness in human pulmonary tuberculosis.

Patients with newly diagnosed, pulmonary tuberculosis had a tuberculin-specific defect in IL-2 production. Mean PPD-induced IL-2 activity was 81.2% lower in patients as compared with healthy tuberculin reactors. PPD-induced expression of T cell IL-2 receptors was 5.9 times less in peripheral blood mononuclear cells of patients with tuberculosis as compared with healthy tuberculin reactors. Furthermore, purified IL-2 failed to correct PPD-induced blastogenesis in patients. Suppression by adherent cells was operative in one group of patients; adherent cell depletion increased their T cell production of IL-2 7.2-fold. A second group of patients with low IL-2 production did not have suppressor adherent cells and were clinically distinct, with more extensive disease on chest x ray. The basis for low IL-2 production in such individuals is unknown. Disordered regulation of IL-2 metabolism may be a key feature in the depressed cellular immune response of tuberculosis.

Bacterial Proteins↗
PubMed1986

Concurrent enhancement of monocyte immunoregulatory properties and effector functions by recombinant interferon-gamma.

Interferon-gamma is a critical factor in the activation of several mononuclear phagocyte effector and immunoregulatory properties. However, it remains uncertain if IFN-gamma is capable of concurrent activation of both functions in the same cell population. Plastic adherent mononuclear cells (80-98% MN by cytochemical criteria) were cultivated in the absence or presence of recombinant interferon-gamma (rIFN-gamma, 0.1-100 U/ml) for 48 hr. MN surface DR antigen was assessed by flow cytometry (EPICS V) after staining with monoclonal antibodies OKIa1 or L243. Exposure to rIFN-gamma (100 U/ml) increased MN surface DR antigen (mean fluorescence intensity) by 80 +/- 20% (P less than 0.01) and 121 +/- 52% (P less than 0.001), respectively, compared to untreated cells. The increase in DR antigen was maximal at 100 U/ml, dependent on protein and RNA synthesis and blocked by agents that increase cAMP levels. IL-1 activity was determined in the mouse thymocyte assay; rIFN-gamma (100 U/ml) increased IL-1 activity in the supernatants of MN cultured in medium alone from 0.5 +/- 0.2 to 7.8 +/- 4.7 U/ml (P less than 0.05), and lipopolysaccharide-stimulated MN from 20.4 +/- 19.1 to 71.7 +/- 38.9 U/ml (P less than 0.05). Following rIFN-gamma exposure, MN stimulation of the AMLR was increased at 6 days (29,269 +/- 5224 vs 13,252 +/- 4938 cpm, P less than 0.01). Spontaneous cytotoxicity (SC) and antibody-dependent cell cytotoxicity (ADCC) were studied in a 51Cr release microculture assay using the human lymphoblastoid cell line CCRF-CEM as target. SC by MN increased linearly as a function of log[rIFN-gamma] for effector:target (E:T) ratios of 5:1 (r = 0.95, P less than 0.01) and 10:1 (r = 0.99, P less than 0.01). ADCC by MN increased following rIFN-gamma exposure (100 U/ml) at E:T ratios of 5:1 (22 +/- 13 to 31 +/- 4%, P less than 0.025) and 10:1 (31 +/- 4 to 38 +/- 4%, P less than 0.01). Thus, rIFN-gamma not only activates MN effector function, but has concurrent stimulatory effects on multiple MN properties critical to immunoregulation.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Preliminary characterization of accessory cells in the nonadherent fraction of human blood mononuclear cells.

We investigated why peripheral blood mononuclear cells rigorously depleted of adherent cells by sequential incubation on plastic and nylon wool remained fully responsive to both antigenic and mitogenic signals. Nylon wool nonadherent cells (NWNA) depleted of cells expressing HLA-DR by monoclonal antibody and complement lysis did not respond to tetanus toxoid (TT) or suboptimal concentrations of phytohemagglutinin (PHA). Addition of adherent accessory cells to these NWNA HLA-DR- cells reconstituted the response to stimuli. NWNA, fractionated by discontinuous density gradient centrifugation, contained high density cells which were unresponsive alone to optimal concentrations of both TT and PHA. All the lower density fractions contained cells which were accessory for higher density cell responses to stimuli. The lowest density fraction was approximately 30% monocytes (esterase and peroxidase positive) and less than or equal to 3% B lymphocytes (surface IgG bearing). The other low density fractions contained large granular lymphocytes but rarely monocytes and no B lymphocytes. Depletion of OKT3+, OKM1+, and Leu-11+ cells from lower density cells by monoclonal antibody and complement lysis did not abolish their accessory activity, but depletion of HLA-DR+ cells or gamma irradiation of these cells decreased their accessory activity for PHA and eradicated accessory activity for TT. Thus, the responsiveness of NWNA to soluble antigenic and mitogenic signals is due, in part, to the presence of low density cells which are radiosensitive and phenotypically HLA-DR+ OKT3-OKM1-Leu-11-. Accessory activity in NWNA seems to reside, therefore, in a cell which is not a typical monocyte, natural killer cell, nor B or T lymphocyte.

Antibodies, Monoclonal↗
PubMed1986

Staphylococcal protein A primed leukocytes enhance the autologous mixed lymphocyte reaction.

Human peripheral blood mononuclear cells (PBMC) were preincubated for 3 days in medium alone or with various mitogens then washed and irradiated. The preincubated cells then were cultured with autologous T-cells in an autologous mixed lymphocyte reaction (AMLR). Staphylococcal protein A (SPA) pretreatment of PBMC enhanced autologous T-lymphocyte proliferation from 1375 +/- 321 cpm (mean +/- SEM untreated PBMC) to 42,467 +/- 7,985 cpm (SPA primed PBMC) (p less than 0.01). The ability of SPA treated PBMC to enhance the AMLR was not simply a reflection of their proliferation in preculture, as PBMC precultured with phytohemagglutinin and concanavalin A showed greater proliferation than SPA-treated PBMC yet only minimally enhanced the AMLR. Kinetic studies and pre-exposure of PBMC to graded doses of gamma radiation showed that SPA augmentation of the AMLR was mediated by 2 components which differed in kinetics and radiosensitivity. Although incubation of PBMC with SPA did not increase the percentage of cells with detectable surface Ia antigen, SPA did increase the density of Ia in the preincubated cells. Cell separation studies revealed that SPA enhancement of the AMLR was not mediated by T-cells, but was mediated by a non-adherent non-E-rosetting fraction of cells. SPA enhancement of the AMLR was associated with an increased Ia density in the stimulator population but not with an increase in Ia positive cells and was mediated by proliferation-dependent and proliferation-independent mechanisms.

Antigens, Surface↗
PubMed1986

Left-sided endocarditis due to Pseudomonas aeruginosa. A report of 10 cases and review of the literature.

Ten confirmed cases of left-sided endocarditis due to Pseudomonas aeruginosa were reported in detail and the English literature was reviewed. In recent years, venous access (usually illicit) has been the major predisposing factor to this infection and abuse of pentazocine and tripelennamine has been particularly associated with endocarditis due to this organism. This infection involves previously damaged as well as normal valves. The development of congestive heart failure did not adversely affect the prognosis of this infection. However, the development of azotemia was associated with a greater likelihood of a fatal outcome. In the current series, deaths were due to uncontrolled infection. This often occurred despite inhibitory and bactericidal activity in serum generally considered adequate for treatment of endocarditis. Medical treatment alone rarely produced cure of infection. Our experience with a high frequency of major vessel embolization (4/10) and the improved survival after medical/surgical treatment suggests that prompt valve replacement combined with high doses of an aminoglycoside plus carbenicillin or ticarcillin provide the best opportunity for successful outcome in patients with left-sided endocarditis due to P. aeruginosa.

Adult↗
PubMed1986

Differential contribution of chemotaxins and opsonins to neutrophil-mediated killing of Schistosoma mansoni larvae.

In neutrophil-mediated killing of schistosomula, antibody and serum complement serve two functions: (i) opsonization of the target pathogen and (ii) generation of cell-activating, chemotactic peptides. We studied neutrophil-mediated schistosomulum killing in experiments designed to isolate these functions of antibody and complement in the cell activation response of neutrophils to external pathogens. Schistosomula opsonized by antibody or antibody plus complement induced neutrophil-mediated killing, while complement-opsonized larvae did not. Antibody enhancement of cell-mediated killing correlated with increased cell-to-parasite adherence, while cell-mediated killing in the presence of fresh normal human serum (providing chemotactic factor stimulation and complement opsonization of larvae) demonstrated a dissociation between neutrophil adhesive and killing responses. Exogenous chemotactic stimuli were found to enhance significantly neutrophil-mediated killing of both opsonized and unopsonized larvae. Experiments involving parabiotic chambers confirmed that chemotactic-factor-stimulated neutrophils may cause significant parasite mortality without direct cell-parasite contact. In further analysis of the neutrophil response to surface and fluid-phase stimulation, release of neutrophil cytotoxic mediators was found to vary according to the type of stimulus provided: cell exposure to either larvae opsonized by antibody plus complement or to chemotactic factors provoked low-to-moderate cell release of superoxide anion, granule enzymes, and arginase; when opsonic and chemotactic stimuli were combined, a greater-than-additive secretory response was noted. Under such maximal stimulation, oxidative and nonoxidative mediators were synergistic in effecting neutrophil-mediated parasite killing. The primary function of complement in cell-mediated parasite killing appears to be to promote chemotactic-factor-mediated cellular release of toxic agents and not cell-target linkage, whereas antibody-mediated adherence is associated with concurrent cellular activation. Both neutrophils adherent to the antibody-opsonized schistosomulum and chemotactic-factor-stimulated cells (adherent and not adherent to the parasite) appear to contribute significantly to its demise.

Adhesiveness↗
PubMed1986

Increased interleukin-1 production and monocyte suppressor cell activity associated with human tuberculosis.

Interleukin-1 (IL-1) production by blood monocytes and blastogenesis produced by tuberculin purified protein derivative (PPD) in blood T lymphocytes were examined in patients with pulmonary tuberculosis. Monocytes were isolated from blood mononuclear cells by plastic adherence, and IL-1 activity was determined in the mouse thymocyte proliferation assay. Monocytes from patients with tuberculosis produced significantly higher activities of IL-1 than did those from healthy tuberculin reactors when stimulated with lipopolysaccharide (LPS) (patients, 56.1 +/- 20.0 U/ml; healthy control subjects, 7.3 +/- 1.7 U/ml; p less than 0.05) or PPD (patients, 28.1 +/- 7.2 U/ml; healthy control subjects, 9.5 +/- 2.9 U/ml; p less than 0.05). In contrast, PPD-induced blastogenic responses in peripheral blood mononuclear cells (PBMC) from the patients were lower than those from healthy subjects (patients, 4,506 +/- 1,145 cpm; healthy control subjects, 14,655 +/- 2,240 cpm; p less than 0.005), and IL-1 production by monocytes showed a positive correlation with monocyte suppressor activity for PPD-induced blastogenesis. Moreover, exogenous IL-1 was capable of suppressing antigen-induced blastogenesis of PBMC from healthy subjects. These data suggest that monocytes from patients with pulmonary tuberculosis are activated to produce or secrete increased levels of IL-1 and that IL-1 may be a mediator of suppressor cell function.

Adult↗
PubMed1986

Inhibition of human lymphocyte proliferation by ultraviolet radiation: effects of ultraviolet B (290 to 320 nm) on T-lymphocytes, monocyte accessory function, and induction of suppressor mechanisms.

In vitro exposure of peripheral blood lymphocytes (PBLs) to doses of ultraviolet radiation (UVR) achievable during recreational sun exposure produces profound inhibition of lymphocyte blastogenesis. This study demonstrates that this inhibition is mediated by a direct dose-dependent effect on populations enriched for T-lymphocytes and is reversible after incubation of responder cells with phytohemagglutinin (PHA). In contrast, monocyte accessory function for both antigen- and mitogen-induced proliferation is relatively unaffected by in vitro exposure to UVR at doses up to 30 mJ/cm2. Exposure of PBL to UVR also results in the induction of a suppressor mechanism that inhibits the proliferation of unirradiated PBLs. In vitro exposure of human blood cells to UVR may provide a valuable tool for examining the cellular basis for the immunosuppressive effects of UVR.

Adult↗
PubMed1986

Immune dysregulation in human tuberculosis.

Hyporesponsiveness to mycobacterial antigens occurs in some patients with tuberculosis. Active immunosuppression by monocytes, T-lymphocytes, and serum is evident and may be a critical factor in anergy. The molecular basis for depressed responsiveness to tuberculin antigens is uncertain, but may involve aberrant surface expression of the HLA-DR gene product on adherent mononuclear cells and abnormalities in immune induction and the cytokine cascade.

Blood Bactericidal Activity↗
PubMed1986

Spontaneous production of a suppressor factor by the human macrophage-like cell line U937. I. Suppression of interleukin 1, interleukin 2, and mitogen-induced blastogenesis in mouse thymocytes.

The human macrophage-like cell line U937 spontaneously produced a nondialyzable factor that inhibited interleukin 1 (IL 1), interleukin 2 (IL 2), and phytohemagglutinin (PHA)-induced blastogenesis in mouse thymocytes. The suppression by U937 supernatant factor occurred independently of the concentration of IL 1 or PHA, indicating that it was noncompetitive. The U937 suppressor factor was not cytotoxic for thymocytes, nor did it affect the spontaneous proliferation of T lymphoblastoid cell lines and U937. Physicochemical characterization showed that the U937 suppressor factor was nondialyzable, partially inactivated by heat treatment (56 degrees C), ammonium sulfate (67% saturation) precipitable, sensitive to pH 2.5, and resistant to freeze-thawing. Molecular weight of the factor inhibiting co-mitogenic IL 1 activity was approximately 85,000, as estimated by gel filtration. The U937 cell line may provide a model for the study of mechanisms and mediators of immunosuppression by mononuclear phagocytes.

Animals↗
PubMed1986

Direct stimulation of monocyte release of interleukin 1 by mycobacterial protein antigens.

We examined stimulation of monocyte (MN) release of interleukin 1 (IL 1) by soluble microbial products. MN from tuberculin skin test nonreactive donors incubated with PPD (100 micrograms/ml) released IL 1 activity of 80.5 +/- 33.9 U/ml (mean +/- SD, n = 6), similar to that induced by optimal concentrations of LPS (76.4 U/ml). OKT3-reactive cells were not required for this process. PPD-stimulated IL 1 release by MN did not appear to be due to endotoxin contamination, as 1) PPD contained 0.01% endotoxin, 2) MN incubated in LPS (0.1 micrograms/ml) produced 19.5 +/- 13.9 U/ml, significantly less than PPD (p = 0.03), and 3) addition of polymyxin B (12.5 micrograms/ml) abrogated IL 1 production in response to LPS (0.1 microgram/ml) but had no significant effect on PPD induction of IL 1. Antigen 5, a partially purified cytoplasmic antigen of Mycobacterium tuberculosis, had similar IL 1-inducing effects. Arabinogalactan (a mycobacterial polysaccharide), streptolysin O, and tetanus toxoid did not. Thus, mycobacterial protein antigens directly stimulate MN to release IL 1. This property may be central to the response of the naive host to mycobacterial infection and may play a pathophysiologic role in tuberculosis.

Animals↗