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Peripheral mononuclear cells (MNC) from patients with systemic lupus erythematosus (SLE) are hyporesponsive in vitro. In order to study the role of mononuclear phagocytes (m phag)in regulating the in vitro responses of autologous lymphocytes, the MNC from 16 SLE patients (eight active, eight inactive) and 14 healthy controls were stimulated in vitro with PHA or dsDNA. The proliferative response to PHA was tested by ³H-thymidine incorporation on day 4 and the response to dsDNA using a specific haemolytic plaque assay. Indomethacin, an inhibitor of prostaglandin (PG) synthesis by m phag, was added into the cultures to test the presence of suppressive m phag acting through a PG-mediated pathway. Indomethacin augmented the proliferative response to PHA in active SLE cultures and not in inactive SLE or controls. In six of 13 SLE cultures, dsDNA totally or partly suppressed anti-dsDNA plaque-forming cell (PFC) generation. Indomethacin restored or enhanced the PFC response to dsDNA in active SLE and not in inactive SLE or controls. M phag depletion by plastic adheretice prevented the effects of indomethacin. These results show that m phag exerting a suppressive activity on PHA-induced lymphocyte proliferation and on anti-dsDNA antibody production are found in cultures from active SLE and generally rot in inactive SLE or healthy individuals. PHA being primarily a T-cell stimulator, the m phag suppressive activity observed in PHA-stimulated cultures is exerted on T cells. On the other hand, in two active SLE cultures depleted of T cells by OKT3 antibody, indomethacin still could enhance the PFC response to dsDN A, showing that in vitro suppressive m phag can act directly on B cells from patients with active SLE. [ABSTRACT FROM AUTHOR]

Alveolar macrophage chemotaxis was measured in 129 individuals--13 normal volunteers, 15 tumour free patients with recent bronchopulmonary infections, 10 patients with chronic bronchitis, 29 patients with endothoracic sarcoidosis, 48 patients with primary bronchial carcinoma and 14 patients with pulmonary metastases from various origins. Chemotaxis was tested in the presence of either zymosan activated autologous serum, N-formyl-methionine-leucyl-phenylalanine (F-Met-Leu-Phe), or zymosan activated human AB serum. Alveolar macrophage chemotaxis was significantly less in patients with bronchial carcinoma than in healthy volunteers (p less than 0.01). Chemotaxis was significantly more depressed in samples obtained from the neighbourhood of the tumour than in samples from the opposite lung. Defective chemotaxis was also found in patients with sarcoidosis. In contrast, the presence of lung metastases did not affect chemotaxis. A recent bronchopulmonary infection was associated with significantly increased (p less than 0.02) chemotaxis in tumour free patients but not in patients with a primary lung tumour. The findings suggest that an intrinsic functional defect of alveolar macrophages might favour the development of bronchogenic carcinoma. [ABSTRACT FROM AUTHOR]

Tiaramide hydrochloride (THC) is a new basic, non-steroidal, anti inflammatory drug. Its anti-anaphylactic action has been investigated using rat mast cells. It was found that THC exerts a strong inhibitory action on antigen induced and compound 48/80-induced histamine release from rat peritoneal mast cells in a fluorometric assay. Compound 48/80-induced vasodilatation in rat skin is inhibited by prior intradermal injection of THC, as measured by blueing of skin due to intravascular Evans blue dye. THC also inhibits radio-labeled serotonin release from compound 48/80-challenged rat mast cells. In these experimental systems a similar action was exerted by disodium cromoglycate, but higher drug concentrations were needed. Further studies are needed to determine the exact mode of action of this drug and its eventual clinical use in the field of allergic diseases. [ABSTRACT FROM AUTHOR]

Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The aim of this retrospective study was to evaluate, during a 6 yr period, the prevalence and severity of bronchopulmonary side-effects in RA patients treated with MTX. A cohort of 130 RA in-patients (106 women, 24 men) treated with MTX was studied for the occurrence of respiratory adverse events. Adverse bronchopulmonary side-effects were observed in 12 patients (two men, 10 women), with a mean disease duration of 15 yr. Only three patients had previously suffered from pulmonary disease. MTX treatment duration was between 1 month and 4.5 yr. The diagnosis was that of hypersensitivity pneumonitis (HSP) in four cases, non-HSP pneumonitis in five patients with one case of Pneumocystis carinii infection, and bronchitis in three cases. The initial respiratory symptoms were not discriminatory between the different conditions. Risk factors were not identified for the occurrence of HSP. HSP always occurred in the first 5 months of treatment. Two patients with HSP died, and another patient with opportunistic infection underwent tracheostomy. HSP represents a potentially lethal side-effect in RA patients treated with MTX. Improved education of patients and physicians should certainly lead to a reduction of both the prevalence and severity of pulmonary side-effects during MTX therapy in RA. [ABSTRACT FROM PUBLISHER]

The synthesis of factors that monitor the expression of the Thy-1 cell surface component by marker-negative precursor cells requires an intact left cerebral cortex, whereas the activity of sodium diethyldithiocarbamate, an immunoptentiator that increases this synthesis, seems to require an intact right neocortex. These results suggust a role for the cerebral cortex in the coordinated interregulation of lymphocyte subclasses. The finding extends previous information suggesting relationships between the central nervous system and the T-cell arm of the immune system. The synthesis of factors that monitor the expression of the Thy-1 cell surface component by marker-negative precursor cells requires an intact left cerebral cortex, whereas the activity of sodium diethyldithiocarbamate, an immunoptentiator that increases this synthesis, seems to require an intact right neocortex. These results suggust a role for the cerebral cortex in the coordinated interregulation of lymphocyte subclasses. The finding extends previous information suggesting relationships between the central nervous system and the T-cell arm of the immune system. [ABSTRACT FROM AUTHOR]

The effects of eight antitumoral drugs known to cause anaphylactoid side effects in clinical use were studied in dogs. Blood pressure, heart rate, and blood and plasma histamine levels were monitored. L-asparaginase, methotrexate, 5-fluorouracil, bleomycin, and cisplatin had no effect on these parameters. Doxorubicin, Vehem (teniposide), and Vepeside (etoposide) induced hypotension, tachycardia, and a rise in histamine levels. In the cases of Vehem and Vepeside, the excipient (respectively, cremophor EL and tween 80) induced the same effects. These agents, like elliptinium, which had been previously studied, induce nonspecific histamine release--unlike the other drugs studied. The mechanism of clinically observed anaphylactoid side effects is discussed in the light of these findings. [ABSTRACT FROM AUTHOR]