Protection of young rats from acute Trypanosoma cruzi infection by interferon-gamma given to their mothers during pregnancy.

We investigated whether administration of interferon-gamma (IFN-gamma) to pregnant rats, infected or not with Trypanosoma cruzi, was likely to protect their offspring from trypanosomal infection. Upon mating with syngeneic sires, four groups of 70-day-old female 1 rats were subjected to one of the following procedures: treatment with recombinant rat (Rr)IFN-gamma 50,000 IU/rat five times/week for three weeks; infection with 1 x 10(6) trypomastigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-gamma treatment as given to the former group; the same protocol but IFN-gamma injections being replaced by injection with physiologic saline.

In vivo protective effect of the lectin from Canavalia brasiliensis on BALB/c mice infected by Leishmania amazonensis.

In vivo administration of Canavalia brasiliensis lectin (at the time of infection, or maintained throughout the infection) reduced the lesions of highly susceptible BALB/c mice infected by Leishmania amazonensis. At the doses used C. brasiliensis lectin (ConBr) does not interfere with penetration or fate of Leishmania in the macrophages in vitro.

Acute and chronic experimental Trypanosoma cruzi infection in the rat. Response to systemic treatment with recombinant rat interferon-gamma.

We examined the effects of recombinant rat interferon-gamma (IFN-gamma) injections on the parasitologic, serologic, immunologic and histopathologic features of acute and chronic experimental Trypanosoma cruzi (T. cruzi) infections in "l" rats. Upon infection at weaning, two rat groups were allocated to receive a 20-day cycle of IFN-gamma injections, 20,000 IU/rat each, which started at 1, and 7 days post-infection (pi).

Clinical healing of antimony-resistant cutaneous or mucocutaneous leishmaniasis following the combined administration of interferon-gamma and pentavalent antimonial compounds.

In an open trial, longer courses of pentavalent antimonials (Sbv) at sub-optimal doses (10 mg/kg body weight), in association with recombinant human interferon-gamma (IFN-gamma) (100 micrograms/m2 of body surface area) were administered, by daily intramuscular injections, to 13 patients with diagnoses of cutaneous or mucocutaneous leishmaniasis unresponsive to Sbv. Four patients presented with large skin ulcers, and 9 had mucosal involvement as the main manifestation, the latter affecting the nose (3 cases), nose and septum (2 cases), nose and oral cavity (1 case), and nose, pharynx and larynx (3 cases). Except for one case with severe involvement of the upper respiratory tract, the lesions were fully resolved by the end of therapy (mean duration 40 +/- 12 [SD] d, range 30-60 d) in the 11 patients who completed therapy.

[Interferon gamma as an immunological strategy for the treatment of human leishmaniasis].

T lymphocytes from patients with visceral leishmaniasis treated in vitro with leishmania antigens are unable to proliferate and to produce gamma interferon. These patients have negative specific skin tests. Opposite results are obtained in patients with another clinical form of the disease named mucocutaneous leishmaniasis, in which both tests are positive.

Lepromatous leprosy treated with recombinant interferon gamma: cutaneous histologic changes.

We report on the histologic changes occurring in single cutaneous lesions, from six active lepromatous patients, 1 week following the administration of three daily intradermal injections, 35 micrograms each, of recombinant interferon gamma (rIFN-gamma). Except for a strong induration at the injection site, rIFN-gamma produced no adverse systemic reactions and was able to promote a remarkable influx of T-lymphocytes, mononuclear phagocytes with large nuclei, nonvacuolated cytoplasm, and reduced lysozyme reactivity. Furthermore, despite no clear-cut reduction of mycobacterial dermal burden, bacilli showed a clear increase in the granular appearance.

Interferon induction by Lactobacillus bulgaricus and Streptococcus thermophilus in mice.

This study investigates the effect of intraperitoneal injection of L. bulgaricus and S. thermophilus on interferon production by Swiss mice.

Tumor necrosis factor (cachectin) in human visceral leishmaniasis.

High tumor necrosis factor-alpha (TNF alpha) levels were present in the serum of 24 of 28 active visceral leishmaniasis (VL) patients (142.9 +/- 113.9 pg/ml, mean +/- SD), whereas levels were not elevated in 26 of 30 patients with cryptic leishmanial infection (16 asymptomatic, 4 with self-healing subclinical infection, and 10 posttreatment VL cases).

Correlation between the biological and therapeutic effects of interferon-alpha in low-grade nodular non-Hodgkin's lymphoma: lack of in vivo down-regulation and reduced affinity of IFN-alpha receptors in unresponsive patients.

We investigated the correlations between the biological effects of interferon-alpha (IFN-alpha) and clinical responsiveness in low-grade non-Hodgkin's lymphomas (NHL). In this disease, 40-50% of cases respond to IFN-alpha therapy. Patients with nodular NHL were selected for a phase II trial in which they were treated daily with 9 x 10(6) U of IFN-alpha 2a.

Treatment of visceral leishmaniasis with pentavalent antimony and interferon gamma.

Acute visceral leishmaniasis is associated with an antigen-specific immunosuppression of mononuclear cells as evidenced by defective in vitro production of interferon gamma. We evaluated treatment with recombinant human interferon gamma in combination with conventional pentavalent antimony therapy in patients with visceral leishmaniasis. Six of eight patients with visceral leishmaniasis (mean duration, 17 months) that had been unresponsive to multiple courses of pentavalent antimony responded to treatment with recombinant human interferon gamma (100 to 400 micrograms per square meter of body-surface area per day) in addition to pentavalent antimony (20 mg per kilogram of body weight per day) for 10 to 40 days.

Scintigraphic study of radiolabelled interferon-alpha in osteosarcoma patients.

Interferon-alpha is currently under evaluation as an antineoplastic agent in several types of tumour. Despite its clear in vitro effects, the effectiveness of interferon in vivo is limited. To assess whether this discrepancy reflects pharmacokinetic limitations, the authors analysed interferon distribution in 2 osteosarcoma patients by scintigraphy using 123I-interferon-alpha-2a.

Effect of interferon-alpha on the expression and release of the CD23 molecule in hairy cell leukemia.

Hairy cells are stimulated to DNA synthesis by low molecular weight B cell growth factor (LMW-BCGF) and this proliferative response is suppressed by interferon (IFN)-alpha, both in vitro and in vivo. The suggestion that the CD23 molecule (Fc epsilon II receptor) might be involved in the signalling pathway of LMW-BCGF prompted us to study the expression of this molecule on hairy cells and its modulation by IFN-alpha. By flow cytometry and direct binding experiments with anti CD23 monoclonal antibodies, the presence of the CD23 antigen was detected in 7 of 12 cases tested, on variable percentages of cells, ranging from low to medium expression.

Expression of the B8.7 antigen on hairy cells and relation with the LMW-BCGF response.

Hairy cells are classified as B cell tumors at a preplasma cell stage of differentiation and are believed to represent cells undergoing a switch process. These cells are stimulated in vitro to DNA synthesis and multiplication in the presence of the lymphokine LMW-BCGF. We have tested the level of expression on these cells of the newly described B8.

Human recombinant gamma-interferon stimulates proliferation and inhibits collagen and fibronectin production by human dental pulp fibroblasts.

Human recombinant-gamma-interferon was tested on human dental pulp fibroblast activity in vitro. Fibroblast proliferation was estimated by a colorimetric test. Type I and type III collagens and fibronectin were quantified by radioimmunoassay in culture supernatant from confluent fibroblasts.

Serum interferon activity of patients with leishmaniasis.

Serum from a significant proportion of 29 cutaneous and 12 mucocutaneous leishmaniasis patients exhibited interferon activity in a cytopathic assay: positive tests were obtained for 24.1% and 41.7% of the patients, respectively.

Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: do cytokines trigger off exacerbations?

We have carried out a longitudinal study of interferon (IFN) and tumor necrosis factor (TNF) using a whole-blood mitogen stimulation assay in 20 multiple sclerosis (MS) patients and in a healthy control group. We set up individual profiles and the results were quite constant for each individual, both in healthy donors and in the patients in remission. Before exacerbations, however, we found an increase of IFN-gamma and TNF production preceding clinical symptoms by a maximum of 2 weeks.

Action of interferon-alpha on hairy cell leukemia: expression of specific receptors and (2'-5')oligo (A) synthetase in tumor cells from sensitive and resistant patients.

IFN-alpha induces tumor regression with a high percentage of complete remissions in hairy cell leukemia. We have recently reported that hairy cells express specific IFN-alpha receptors which are down-regulated upon therapy. We show here that the activity of 2-5 A synthetase, an IFN-induced enzyme, is 2 to 7-fold stimulated in hairy cells from responsive patients within 12-24 h after the first IFN dose.

Human lung cancer nodules in organotypic culture: no evidence of correlation between the antiproliferative effects of interferons and the induction of 2',5'-oligoadenylate synthetase.

Alveolar II pulmonary tumor cells (A549), maintained in continuous tridimensional organotypic culture, were used in an attempt to investigate whether there could be a relationship of the 2',5'-oligoadenylate (2,5A) synthetase pathway to the antiproliferative activity of interferons (IFNs) in this particular tumor cell model. IFN-alpha 2, -beta and -gamma were used separately and in combinations. IFN-alpha 2 and -gamma demonstrated an inhibitory effect on the nodule growth, whereas IFN-beta did not.

From old results to new perspectives: a look at interferon's fate in the body.

In a previous report, we presented preliminary data on interferon-alpha A (IFN-alpha A) pharmacokinetics through the simultaneous study of distribution of the radiolabeled protein by numerical dynamic scintigraphy and the trichloroacetic acid (TCA)-precipitable radioactivity in whole blood and serum, as well as the radioactivity linked to blood mononuclear cells. The interferon preparation then used was contaminated with free iodine which gave parasite images and counts. Here we present further analysis of those data, enlightened by additional information collected in new studies with interferon preparations without free iodine.

Proliferative response of hairy cells to B cell growth factor (BCGF): in vivo inhibition by interferon-alpha and in vitro effects of interferon-alpha, -beta, and -gamma.

Hairy cell leukemia (HCL) is a pre-plasma B cell tumor which responds to interferon (IFN)-alpha therapy. In vitro, B cell growth factor (BCGF) can induce proliferation of hairy cells. We have investigated the effect of in vitro and in vivo treatments with different recombinant IFN on the capacity of hairy cells to proliferate in response to human BCGF.

The effector function of platelets is induced and regulated by T lymphocytes.

The demonstration of effector functions of platelets in parasitic diseases raised the question of their possible regulation by T lymphocytes. Normal human platelets, treated with culture supernatants from antigen- or mitogen-stimulated CD4+/CD8- T cells, developed the capacity to kill young larvae of Schistosoma mansoni, in the absence of antibodies. The presence of IFN gamma in the lymphocyte supernatants, the neutralization by monoclonal anti-IFN gamma antibody, and the direct inducer effect of recombinant IFN gamma, clearly identify this lymphokine as one of the stimulator factors.

Potentiation of antiproliferative activity by mixtures of human recombinant IFN-alpha 2 and -gamma on growth of human cancer nodules maintained in continuous organotypic culture.

Alveolar II pulmonary tumor cells (A549 cells) maintained in continuous tridimensional organotypic culture were used to evaluate the eventual potentiation effect of mixtures of recombinant human interferon-alpha 2 and -gamma on growth inhibition of the tumor nodules. A continuous 45 day treatment (interferon renewed three times a week) with 10, 10(2) or 10(3) U/ml of IFN-alpha 2 or -gamma combined with a fixed high dose (10(3) U/ml) of either IFN-alpha 2 or -gamma resulted in an additive or synergistic growth inhibition according to the doses used. There was a close dose-effect relation, the percentage of inhibition increasing proportionally to the variable IFN doses added to the fixed high dose; moreover, the growth inhibition effect occurred earlier with the mixtures than with IFNs used separately.

In vivo and in vitro induction of (2'-5') oligoadenylate synthetase by human interferons in leukocytes from healthy donors and patients with renal cancer and hairy cell leukemia.

The effect of in vivo administered interferon-alpha (IFN-alpha) on 2-5-oligoadenylate (A) synthetase activity of peripheral blood mononuclear cells (PBMC) was compared in patients with hairy cell leukemia and renal cell cancer. Basic levels of this enzyme varied from donor to donor, but mean levels were not significantly different in patients with renal cell cancer or hairy cell leukemia compared to healthy donors. After a single injection of 3 x 10(6) IU IFN, these basic levels rose 2- to 8-fold within 12-24 h post-injection and reverted to pretreatment levels after 48 h.