Lysis of pulmonary fibroblasts by lymphokine (IL-2)-activated killer cells—a mechanism affecting the human lung microenvironment?

In this study we investigated whether IL-2-activated killer cells may bind and exert lytic activity against non-transformed lung fibroblasts. We demonstrated that human lymphokine-activated killer (LAK) cells generated in vitro following incubation with recombinant IL-2 of either peripheral blood mononuclear cells (PB-LAK) or lymphocytes obtained from bronchoalveolar lavage (BAL-LAK), but not resting cells, can lyse normal lung fibroblasts obtained from transbronchial lung biopsies in a 4-h ⁵¹Cr release assay. Both autologous and allogeneic fibroblasts were consistently lysed by LAK cells, thus suggesting that the phenomenon we observed is not MHC-restricted. Since fibroblasts can bind IL-2 through specific receptors, we evaluated whether long-term culture with rIL-2 could modulate the susceptibility to lysis of target cells. Our data showed that autologous fibroblasts were more resistant to lysis than allogeneic fibroblasts when they were cultured with rIL-2. Since LAK cells have been demonstrated to release a series of different immunomodulatory cytokines, we evaluated the effect of short-term incubation of fibroblasts with different factors, including IL-1, IL-2, IL-3, IL-4, IL-6, tumour necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), on the binding and the lysis mediated by LAK cells. These cytokines were not directly cytotoxic on fibroblasts. Only IFN-γ was found to have a significant protective effect against the lysis. Our data support the concept that a self-directed cytotoxicity against pulmonary fibroblasts is generated during lymphocyte activation with rIL-2.     

Long-Term Results of Hybrid Therapy in Patients with Atrial Fibrillation Who Develop Atrial Flutter During Flecainide Infusion

The flecainide infusion test has been proposed to screen candidates for hybrid pharmacological and ablation therapy. We report the long-term follow-up of 154 consecutive patients with paroxysmal or persistent atrial fibrillation (AF) who developed atrial flutter (AFL) during flecainide infusion (IC AFL), treated with inferior vena cava-tricuspid annulus isthmus catheter ablation and oral flecainide (hybrid therapy). Over a mean of 54.1 ± 13.1 months 82 patients (53%) remained free of AF and AFL. Flecainide was discontinued because of adverse effects in 6 patients (4%). A history of persistent AF, and the documentation of ≥1 spontaneous AFL episode before the flecainide test were independent predictors of successful hybrid therapy. In patients with paroxysmal AF without documented spontaneous AFL, the long-term efficacy of hybrid therapy was 38.5% (P = 0.03). The flecainide infusion test reliably detects candidates for hybrid therapy. The efficacy of this therapy is maintained over the long-term with a high patient compliance.     

FUNCTIONAL ANATOMY OF CAVERNOUS HELICINE ARTERIOLES IN POTENT SUBJECTS

Purpose

We investigated the morphological and functional features of cavernous helicine arterioles in male potent subjects.

Materials and Methods

Ten young men reporting normal rigid erections which were confirmed by polysomnographic recording underwent power Doppler sonography of the cavernous helicine arterioles during flaccidity, after intracavernous injection of alprostadil, and after subsequent genital and audiovisual sexual stimulation.

Results

During flaccidity the helicine arterioles were never detected by power Doppler imaging while they became evident in all cases after alprostadil injection. They usually originated from the cavernous artery forming an acute angle and showed 3 orders of ramifications. Systolic and diastolic flow was present. After genital and audiovisual sexual stimulation, and achievement of maximum rigidity, the helicine arterioles were still evident but with only 1 or 2 orders of distal ramifications. Only systolic flow was present. During penile tumescence the helicine arterioles disappeared in all cases.

Conclusions

Using power Doppler sonography it is possible to investigate the functional anatomy of the cavernous helicine arterioles during the various phases of the erectile cycle. Our preliminary study suggests that the helicine arterioles are functionally inactive during penile flaccidity while they are activated during penile tumescence and continue to supply blood to the corpora also during maximum penile rigidity.