Human as well as canine and rat polymorphonuclear cells (PMN) were separated from whole blood by centrifugation. Two-step discontinuous Percoll gradients with distinct different densities were used. The chemiluminescence properties of the isolated PMN and of phagocytes in small quantities of whole blood were compared in luminol-enhanced assays after stimulation with various agents: non-opsonized zymosan (3.5 g/l), phorbol myristate acetate (PMA, 2.8 x 10(-6) mol/l), calcium ionophore A 23187 (10(-5) mol/l) and N-formyl-methionyl-leucyl-phenylalanine (FMLP, 3.5 x 10(-6) mol/l). The isolated cells of the three species responded to all of the various stimuli. Species-related sensitivity could be ordered: human greater than canine greater than rat. Response to the various agents in the human cells can be ranked: PMA greater than or equal to A 23187 greater than zymosan greater than FMLP; for the dog: A 23187 greater than PMA greater than zymosan greater than FMLP; and for the rat: zymosan greater than or equal to PMA greater than FMLP greater than or equal to A 23187. Time course and peak maximum response were different upon stimulation in the absence and presence of autologous plasma. Distinct soluble stimuli resulted in maximum responses below the baseline in the whole blood assays with canine (FMLP) and rat (FMLP, A 23187) phagocytes.

Animals↗

PubMedDate not supplied

[Manifestation of neuro-Behçet disease in cyclosporin A therapy].

Behçet's disease is a chronic inflammatory disorder characterized by the triad of oral and genital ulcers and ocular lesions. One of the most life-threatening manifestations results from involvement of the central nervous system, presenting as necrotising meningo-encephalitis, most typically affecting the brain stem, internal capsula and basal brain ganglia. We report on a young Caucasian mate with Behçet's disease (HLA B 51+) and recurrent uveitis, who presented with acute neurologic involvement under CyA therapy 5 years after first diagnosis. At the time of admission MRI showed two high intensity lesions in the brain stem on T1 weighted images enhanced with Gd-DTPA, reflecting active inflammation. Shortly after admission the CyA treatment was stopped and a therapy with high dose steroids and chlorambucil, starting with a dose of 2 mg daily was initiated. This led to improvement of neurologic symptoms, also documented by brain stem evoked potentials and investigations of cerebrospinal fluid, as well as of ophtalmologic symptoms within few days of treatment. Steroids were reduced to a maintenance dose of 12 mg Prednyliden daily. The brain MRI taken 8 weeks after onset of chlorambucil treatment showed the same lesions in the brain stem, with low intensity in the T1 weighted images an no longer enhanced Gd-DTPA uptake. Chlorambucil dose was reduced to 2 mg every second day after 8 months. There was no exacerbation in the follow-up of 12 months. We conclude that a 6-week Chlorambucil therapy consisting of 2 mg/p.o./d led to remission of neurologic involvement firstly evolving under CyA-medication which suggests superiority of chlorambucil as a treatment modality in neurologic as well as ophtalmologic features of the disease.

Adult↗

PubMedDate not supplied

What we have learned from trials of immunomodulatory agents in rheumatoid arthritis: Future directions.

In recent years substantial progress has been made in understanding the mechanisms of inflammation and autoimmunity. In an attempt to interfere with selected stages of the immune response, a variety of biological agents has been designed that specifically targets elements of the immune system. In rheumatoid arthritis (RA), a number of open-labeled clinical trials with immunomodulatory agents, such as monoclonal antibodies or recombinant proteins, has provided encouraging initial clinical results. However, with the recent exceptions of biologics inhibiting the activity of proinflammatory cytokines, randomized, controlled studies have largely failed to demonstrate a significant benefit of these agents over placebo. Nevertheless, the clinical trials have provided an excellent opportunity to test the consequences of interfering with specific interactions involved in immunity. Moreover, from the results and experiences from these studies new therapeutic strategies are constantly emerging. Some new approaches, including the application of agents that target a diverse array of substances such as cytokines, chemokines, enzymes, cell surface molecules involved in adhesion or signaling, and nitric oxide, are currently tested in animal models of human rheumatic diseases. In this article, trials of immunomodulatory agents in RA are reviewed, with an emphasis on what we have learned so far and what we have yet to learn. We will discuss recent advantages in the understanding of the pathogenesis of the disease and delineate new therapeutic approaches for chronic arthritis.

Journal Article↗