Modulation of leucocyte locomotion by interleukin-1.

The influence of interleukin-1 (IL-1) upon leucocyte locomotion in vitro was studied, using either casein or zymosan-activated serum (ZAS) as chemotaxigens. A pre-incubation of polymorphonuclear cells (PMNC) with ultrapure (purity 99%) human IL-1 (1 U/ml) for 2 and 5 h followed by a washing step resulted in a significant decrease in leucocyte locomotion against casein (P less than 0.0005 and P less than 0.01, respectively), but not against ZAS (P greater than 0.1). Moreover, the direct addition of this IL-1 preparation to leucocyte locomotion assays without pre-incubation produced a similar and significant inhibition of leucocyte locomotion directed against casein (P less than 0.05). This inhibitory effect could not be augmented further by higher concentrations of ultrapure IL-1. In order to exclude the effect of possibly contaminating cytokines in the ultrapure IL-1 preparation used, additional assays with recombinant human IL-1 (rIL-1) alpha and rIL-1 beta (1 U/ml) were performed to investigate their influence upon leucocyte locomotion. It was found that both rIL-1 alpha and rIL-1 beta inhibited leucocyte locomotion directed against casein significantly (P less than 0.005). Similar to the previous experiments, leucocyte locomotion could not be further inhibited by higher concentrations (10 U/ml) or rIL-1. Thus, both ultrapure and rIL-1 were found to have the ability to inhibit leucocyte locomotion in vitro.

Arterial aneurysms associated with human immunodeficiency virus (HIV) infection.

The authors report four arterial aneurysms seen in three patients infected by HIV. The aneurysms affected: 1) the left common carotid artery in a young man HIV carrier, 2) the right common carotid artery and the abdominal aorta in a woman with AIDS, 3) the right common carotid artery in a patient with AIDS-related complex. The aetiology was found to be infectious, respectively: 1) staphylococcus epidermidis (certain), 2) tuberculosis or another undetected infection (possible), 3) staphylococcus epidermidis or syphilis (highly probable). A viral arteritis mechanism is also postulated in the second case. If this association of aneurysms with HIV infection is not fortuitous, an increase of aneurysm incidence in HIV infected population is to be expected.

Association of increased lytic effector cell function with high estrogen receptor levels in tumor-bearing patients with breast cancer.

Tumor-bearing patients with breast cancer were assayed for their natural killer (NK) cell activity and for the function of activated cytotoxic T-cells, as assessed by lectin-dependent cellular cytotoxicity (LDCC). Tumor-bearing patients with breast cancer had a significant increase in NK activity and in LDCC, as compared with healthy control individuals. Although the enhanced NK cell activity and LDCC were closely associated with high levels (greater than 31 fmol/mg) of estrogen receptor (ER) content in the primary tumor, no other clinical or histologic correlation between the increase in either parameter of cytotoxic effector cell function could be found. Thus, ER levels greater than 31 fmol/mg might be associated with increased cytotoxic effector cell function in tumor-bearing patients with breast cancer.

Effects of cyclosporin A upon humoral and cellular immune parameters in insulin-dependent diabetes mellitus type I: a long-term follow-up study.

Patients who had been included in a randomized double-blind placebo-controlled trial on the efficacy of cyclosporin A (CyA) in producing remissions in insulin-dependent diabetes mellitus (IDDM) type I were investigated for humoral and cellular immunologic parameters. Whereas metabolic derangement before the initiation of insulin treatment led to small but significant decreases in the percentage of CD4-positive lymphocytes as well as of the activity of natural killer (NK) cells and antibody-dependent cellular cytotoxicity (ADCC), the administration of CyA did not influence any of the immunologic parameters tested, which included proliferative lymphocyte responses to mitogens and alloantigens and serum concentrations of immunoglobulins G, A and M. Thus NK cell activity, ADCC as well as the percentage of CD4-positive lymphocytes returned to normal levels in parallel with the normalization of glycosylated haemoglobin (HbAlc), but were not further influenced in their course by the administration of CyA, as compared with patients receiving placebo. Interferon-induced augmentation of NK cell activity did not differ between patients with IDDM on placebo and those under CyA therapy. All other investigated parameters also remained unchanged during the time of CyA therapy. We conclude that metabolic derangement leads to a reversible disturbance of certain cellular immune functions, but their normalization achieved by insulin treatment and their further course remains uninfluenced by the administration of CyA.

Comparative pharmacokinetics of doxycycline and oxytetracycline in patients with hyperlipidemia.

This study examines the pharmacokinetics of lipophilic drug doxycycline (Vibramycin) and water-soluble antibiotic oxytetracycline hydrochloride (Oxyterracyna) in patients with hyperlipidemia type IIa and type IV according to Fredrickson. Antibiotics were administered orally as a single dose and determined in plasma by a fluorimetric method. The calculations were performed by aid of a computer. Increased concentrations of doxycycline were found; they were higher in type IIa, as compared with type IV. Area under the curve (AUC) and peak concentrations as well as rate constant for elimination in subjects with type IV were significantly elevated; volumes of distribution and total body clearance were markedly diminished. Decreased concentrations of oxytetracycline, area under the curve, peak concentration and rate constant for elimination were observed in patients with type IV. In both types of hyperlipidemia volume of distribution was increased and half-life in patients with type IV was significantly prolonged. The findings show that hyperlipidemia can be an important factor of drug action. Alterations of pharmacokinetics of lipophilic doxycycline and hydrophilic oxytetracycline were contrasting.