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.

Variations in susceptibility to Leishmania amazonensis infection in lines of mice selected for high or low immunoresponsiveness.

The degree of resistance to a local Leishmania amazonensis challenge has been compared in lines of mice obtained by selective breeding for high or low immunoresponsiveness: High and Low antibody responder mice of Selections I and II (HI, HII and LI, LII lines) and high and low responder mice to T mitogen PHA (Hi/PHA and Lo/PHA). The aim of this preliminary study was to focus attention on genetic differences related with well defined immune characteristics. Clear-cut results were obtained, both HI and HII mice developed large and disseminating lesions, the rate of symptom aggravation being faster in HII, while LI and LII proved resistant to parasites, only small and transient lesions being observed for them during a 150 days follow up.

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).

Activity of a platelet protein kinase that phosphorylates fibrinogen and histone in Argentine hemorrhagic fever.

The activity of a platelet protein kinase that phosphorylates the alpha-chain of fibrinogen and the exogenous substrate histone was evaluated in 28 patients with Argentine hemorrhagic fever, grouped into: 13 mild, 6 moderate and 9 severe clinical forms. Blood samples were obtained before treatment with immune plasma, 4 days later and at recovery. Exogenous histone and fibrinogen phosphorylation were assayed with 25 Ci/mmol (gamma-32P)-ATP.

Synergistic effect of interferon-gamma and tumor necrosis factor-alpha on antiviral activity and (2'-5') oligo (A) synthetase induction in a myelomonocytic cell line.

TNF was not observed to have an antiviral effect on either HL60 or U937 cells. However, it did significantly enhance interferon (IFN)-gamma-mediated antiviral activity in U937 cells. Treatment of U937 cells with IFN-gamma enhanced (2'-5') oligo (A) synthetase activity (2.

Secretion of interleukin-6 (IL-6) by human monocytes stimulated by muramyl dipeptide and tumour necrosis factor alpha.

We studied IL-6 gene expression in human monocytes stimulated by muramyl dipeptide (MDP), a synthetic immunomodulator derived from mycobacterial cell walls. In control monocytes, two IL-6 transcripts of 3.4 kb and 1.

Inhibitory effect of interferon-gamma on adenovirus replication and late transcription.

We have previously shown that human interferon-gamma inhibited adenovirus multiplication in vitro in a dose-dependent fashion. This action was previous to capsid proteins synthesis and did not involve virus adsorption nor penetration. In this report we have analysed viral mRNA levels at early (7 hr post infection (p.

Interferon gamma is active on human lymphoblastoid Namalva cells without inducing an antiviral state.

We demonstrate the presence of high affinity receptors specific for interferon-gamma (IFN-gamma) in human lymphoblastoid Namalva cells. The presence of these receptors, whose binding affinity and cross-linking characteristics were not distinguishable from those of the corresponding receptors in sensitive cells, was not consistent with the lack of responsiveness of Namalva cells to IFN-gamma as regards growth inhibition, induction of 2'-5' oligoadenylate synthetase activity and inhibition of virus multiplication. Nevertheless, IFN-gamma enhanced the expression of two genes, HLA class II and c-myc.

Interferon-beta 2 (BSF-2) mRNA is expressed in human monocytes.

We previously have reported the presence of interferon-beta 2 (IFN-beta 2) mRNA in PHA-stimulated human peripheral blood leukocytes (PBL), as well as in nonstimulated cells, although at a lower level. The IFN-beta 2 cloned from a leukocyte library appeared to be similar to that of the fibroblast IFN-beta 2 gene first described in fibroblasts. To assess the nature of the cell population in which the synthesis of IFN-beta 2 takes place, PBL were fractionated in adherent and nonadherent cells.

Recombinant human interferon-gamma inhibits adenovirus multiplication without modifying viral penetration.

We have recently reported that adenovirus replication is inhibited by human recombinant interferon-gamma, but not by recombinant interferon-alpha, in a dose-dependent manner. The aim of this study was to determine whether the antiviral effect of recombinant interferon-gamma could be linked to interferon-induced alteration at the membrane level, inhibiting either adenovirus penetration of or release from WISH cells. Adsorption and penetration were investigated with an 125I-labelled adenovirus binding assay.

Intracellular human gamma-interferon triggers an antiviral state in transformed murine L cells.

Interaction of human gamma-interferon (IFN-gamma) with a cell-surface receptor is known to be essential for the cell to become resistant to viral infection. Here we demonstrate that IFN-gamma, when present inside the cell, is also capable of inducing a permanent antiviral state. Mouse cells transformed with a truncated human cDNA encoding a mature IFN-gamma protein lacking the signal peptide accumulate high levels of intracellular human IFN-gamma.

Recombinant human interferon-gamma inhibits adenovirus multiplication in vitro.

The susceptibility of adenovirus to the inhibitory effect of human interferons in vitro was investigated. We tested recombinant human interferons-alpha 2, -beta 1 and -gamma against adenovirus serotypes 1 and 5 (group C), 3 and 7a (group B), and a wild strain isolated from an acutely ill child who later died. Pretreatment of WISH cells with interferon-gamma for 24 h induced a dose-dependent inhibition of multiplication of all adenovirus strains tested, the TCID50 varying from 25 to 90 IU/ml.

Regulation of human gamma-interferon and beta-interferon gene expression in PHA-activated lymphocytes.

Two interferon (IFN) messengers were synthesized in phytohemagglutinin (PHA)-activated lymphocytes: IFN-gamma mRNA and a messenger hybridizing with the IFN-beta 2 probe. They were induced rapidly and declined at a stage when overall RNA was still efficiently transcribed. The IFN-beta 2 mRNA (15S) present in the lymphocytes was slightly different from its fibroblastic counterpart (14S).

Expression of extracellular and intracellular human IFN-gamma in mouse L cells transformed with the human IFN-gamma cDNA gene.

Cotransformation with a plasmid containing a thymidine kinase gene (pTK2) and a plasmid encoding human IFN-gamma (pTG11) has been used to establish murine L cell lines expressing human IFN-gamma. The HuIFN-gamma gene was present in 30% of the tk+ cell lines and some of these secreted low levels of IFN into the culture medium. Two of the clones obtained after transformation were selected for detailed analysis.

T-cell surface antigens defined by monoclonal antibodies, involved in the induction of human interferon-gamma and interleukin 2.

Monoclonal antibodies specific for human T-cell-differentiation antigens were used to investigate the mechanism of induction of interferon-gamma (IFN-gamma) and interleukin 2 (IL-2). High levels of IFN-gamma, accompanied by IL-2 production, were detected in the lymphocyte cultures stimulated by pan T monoclonal antibodies that were mitogenic. These antibodies recognize an antigen complex Tp 19-29 (a complex of T-cell proteins of 19-29 kDa).

Correlation between endogenous interferon and the clinical evolution of patients with Argentine hemorrhagic fever.

To explore the endogenous interferon levels in patients of Argentine hemorrhagic fever (AHF) with different clinical evolution of the disease, 29 fatal and 33 surviving cases of AHF were analyzed. As previously reported, the titers of endogenous alpha-IFN in patients with AHF are very high, generally between 2,000 and 64,000 IU/ml. Thus far, these are the highest levels of circulating interferon detected in any human viral disease.

Characterization of antibodies against recombinant HuIFN-gamma produced by hybridoma cells.

Balbc/c mice were immunized with purified recombinant E. coli-derived human gamma-interferon (HuIFN-gamma). Their spleen cells were fused with a mouse myeloma cell line (Sp2/0).

SLO4, a new interferon inducer isolated from Klebsiella pneumoniae and Escherichia coli.

A product isolated from Klebsiella pneumoniae and Escherichia coli, coded SLO4, has been shown to be effective in endogenous interferon induction in vivo in mouse when administered IP or IV, and in vitro with human leukocyte cultures. In these two systems induced interferon was defined. The inducer has not yet been characterized but seems not to belong to any components known to be interferon inducers such as viral particles, nucleic acids or endotoxins.

Helper activity for antibody synthesis encoded by mRNA extracted from human peripheral blood mononuclear cells.

Translation products in Xenopus laevis of mRNA from human peripheral blood mononuclear cells were tested for their capacity to replace T cells in the anti-SRBC response of nude spleen cells. When the starting material came from PHA or FCS-stimulated lymphocytes, the translated lymphokines, displaying such a B cell helper activity were found to be encoded by mRNA sedimenting at 6-7S and 13S on a sucrose density gradient. 6-7S mRNA from control, non-stimulated lymphocytes was also able to code for B cell helper activity.

Kinetics of messenger accumulation coding for IFN gamma, related to modifications in the poly(A) RNA population of activated human lymphocytes.

Exposure of human lymphocytes to a mitogen induces the appearance of newly synthesized RNAs and proteins. This study describes the changes in overall synthesis as measured by pulse labelling of PHA treated lymphocytes as well as a qualitative analysis of the protein synthetic patterns "in vivo" and "in vitro". Both the levels of RNA and protein synthesis increase drastically in PHA stimulated cells, while cultures incubated without mitogen remained at background levels.