M Murone

Efficacy of Low-Dose Intermittent Subcutaneous Interleukin (IL)–2 in Antiviral Drug–Experienced Human Immunodeficiency Virus–Infected Persons with Detectable Virus Load: A Controlled Study of 3 IL-2 Regimens with Antiviral Drug Therapy

To evaluate the safety and efficacy of 3 regimens of intermittent subcutaneous (sc) interleukin (IL)--2 in a phase 2 study, 61 antiviral drug-experienced human immunodeficiency virus (HIV)--positive patients were randomly assigned to one of the following study arms: antiretroviral therapy (ART) plus IL-2 (12 million IU [MIU] by continuous intravenous infusion, followed by 7.5 MIU twice a day, sc, every 8 weeks); ART plus IL-2 (7.5 MIU twice a day, sc, every 8 weeks); ART plus IL-2 (3 MIU twice a day, sc, every 4 weeks); or ART alone. A significant increase of circulating CD4 cells was observed in IL-2--treated subjects, compared with those given ART alone. Low doses of IL-2 were better tolerated. Despite the incomplete suppression of viral replication, IL-2 with ART did not increase either plasma viremia or cell-associated HIV DNA levels. Low doses of intermittent sc IL-2 induced a stable increase of peripheral CD4 cells that was indistinguishable from those associated with higher, less well-tolerated doses of IL-2.

Dual role of TNF‐α in NK / LAK cell‐mediated lysis of chronically HIV‐infected U1 cells. Concomitant enhancement of HIV expression and sensitization of cell‐mediated lysis

The U937‐derived chronically HIV‐infected U1 cell line and uninfected U937 cell clones were efficiently lysed by both unstimulated (NK) and IL‐2‐stimulated (lymphokine‐activated killer; LAK) peripheral blood mononuclear cells (PBMC) of healthy HIV‐seronegative donors. Pretreatment of target cells with IFN‐γ down‐modulated killing of both U1 cells and two U937 cell clones, and up‐regulated MHC class I expression. In contrast, TNF‐α enhanced the sensitivity of infected U1 cells, but not of U937 cell clones to NK / LAK cell lysis. Co‐cultivation of IL‐2‐stimulated PBMC with U1 cells triggered expression and replication of HIV by cell‐cell contact, and this effect was inhibited by anti‐TNF‐α antibodies (Ab); virus production was partially inhibited by zidovudine. Of interest, anti‐TNF‐α Ab protected U1 cells from LAK cell activity. Thus, TNF‐α can induce HIV expression from chronically infected U1 cells, but also plays an important role in sensitizing these cells to lysis.

Tumor Necrosis Factor α, Interleukin 2, and Soluble Interleukin 2 Receptor Levels in Human Immunodeficiency Virus Type 1-Infected Individuals Receiving Intermittent Cycles of Interleukin 2

HIV-infected individuals with 200-500 CD4(+) T cell/microl were enrolled in a controlled study of three interleukin 2 (IL-2) plus antiretroviral therapy (ART) regimens: (1) continuous intravenous administration of 12 million international units (MIU) of IL-2 followed by subcutaneous high-dose IL-2 (7.5 MIU, twice daily) for 5 days every 8 weeks; (2) high-dose subcutaneous IL-2 for 5 days every 8 weeks; (3) low-dose (3 MIU, twice daily) subcutaneous IL-2 for 5 days every 4 weeks; and (4) ART alone. Serum concentrations of IL-2, soluble IL-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-alpha), and IL-6 were determined. A progressive decrease over time of the circulating levels of IL-2 was observed in individuals receiving the highest doses of IL-2, but not in those belonging to the low-dose arm. Conversely, increased levels of sIL-2R were observed in all cytokine-treated individuals. The levels of TNF-alpha increased in the high-dose IL-2 regimens, but decreased in individuals receiving low-dose IL-2. IL-2-related toxicity was significantly correlated to the peak IL-2 serum levels, and was substantially lower in those individuals receiving low-dose IL-2. In conclusion, intermittent IL-2 administration causes the elevation of peripheral CD4(+) T cells, but also a profound cytokine response and systemic toxicity. The latter was correlated to the peak serum level of IL-2, but not to those of TNF-alpha and IL-6.

Tumor-associated trypsin inhibitor in induced and acquired immunodeficiency. Studies on transplanted and HIV-infected patients.

A new tumor marker, tumor-associated trypsin inhibitor (TATI), was studied in 5 patients who received successful kidney or pancreas grafts and in 30 subjects with antibodies against human immunodeficiency virus. Serum TATI concentrations were very high during the four first days after transplantation. Thereafter the serum levels decreased when the peptide was eliminated through the kidney. Consequently, the urine values were very high. The TATI concentrations of HIV positive subjects were compared with serum levels of HIV antigen and antibody, by Western blotting and determination of peripheral T-lymphocyte subpopulations. The occurrence of high concentrations of TATI in some HIV positive subjects and especially in AIDS patients, suggests that TATI could be useful in exploring physiopathological aspects of severe immunodeficiencies even if TATI levels were not correlated with the commonly used markers of the immune system status. The increased levels of TATI in immunological disorders suggests its possible use in assessing the immune response against cancer.

Automation in urinalysis: evaluation of three urine test strip analysers.

A clinical laboratory evaluation was conducted on the Clinitek Auto 2000, the Super Aution Analyzer and the Urotron RL9 for the determination of glucose, protein, pH, blood, ketone-bodies and bilirubin. Precision of the systems was tested using three commercial control urine materials, and reported as the percentage of times the instrument repeats a certain value. Good repeatability was obtained with all the instruments. Accuracy of the systems was evaluated by comparison with quantitative procedures, and to check agreement between methods yielding semi-quantitative and quantitative results, ranges of acceptability were defined, based on the criteria reported in a previous paper [2]. It was then found that 87.5 to 98.9% of results from the Urotron RL9 and the Clinitek Auto 2000 were acceptable. With the Super Aution Analyzer the level of agreement was apparently lower because of the higher number of concentration steps used by this instrument.

Tumor-Associated Trypsin Inhibitor as a Possible Marker in Male Infertility

The concentrations of tumor-associated trypsin inhibitor (TATI) in the seminal plasma of infertile males was studied. The TATI levels in seminal plasma were not correlated with either sperm count or ejaculate volume. High levels were observed in some men with unexplained infertility and high or normal sperm counts, whereas normal levels were observed in males with antisperm antibodies. The concentrations in seminal plasma were stable in the same subjects. These results suggest that TATI may be an important marker of reproductive pathology in men.