DIMINISHED IL-2-INDUCED GAMMA-INTERFERON PRODUCTION BY UNSTIMULATED PERIPHERAL-BLOOD LYMPHOCYTES IN RHEUMATOID ARTHRITIS

A diminished gamma-interferon (IFN-gamma) production by T cells from patients with rheumatoid arthritis (RA) in response to autologous stimulation coincides with a defective regulation of Epstein-Barr virus (EBV) transformation and is in part due to monocyte-produced interleukin-1 (IL-1) inhibitor and prostaglandins. Since IL-2 can act directly on unstimulated T-cells to induce IFN-gamma production we have now examined the effect of recombinant IL-2 (rIL-2) on purified resting T lymphocytes from RA patients. Treatment with rIL-2 (25 U/ml) of lymphocytes from 15 controls led to an increased production of 72-h supernatant EBV-inhibitory activity (19±4% SE without; 48±7% with rIL-2), but had only minimal or no effect on gamma-interferon production by E-rosetting lymphocytes from 15 patients with active RA. This defect could not be corrected by adding indomethacin to RA culture

[HDL inhibit cytokine production in a mouse model of urate crystal-induced inflammation].

Objectives: To evaluate whether high density lipoproteins (HDL) affect monosodium urate (MSU) crystal-induced inflammation in the murine air pouch model. Methods: MSU crystals were prepared by Denko's method and sterilized by heating at 180°C for 2 h before each experiment. Human HDL were isolated from peripheral blood of healthy volunteers. MSU crystals (2 mg in 1 ml of PBS) were injected into subcutaneous air pouches in mice in the presence or absence of HDL (0.1 mg). Negative control pouches received 1 ml of PBS. To recover pouch fluid, the pouches were washed with 2 ml of PBS after the animals were sacrificed. The leukocyte count in the lavage fluids was obtained using a hemocytometer and differential leukocyte count was determined by May-Grünwald-Giemsa staining. IL-6, KC, CCL2 and TNF-α levels were measured in exudates by ELISA. Results: MSU crystals increased the number of leukocytes and the neutrophil migration, as well as the concentrations of IL-6, KC and CCL2 in pouch fluids, while the TNF-α levels were not detectable. The treatment with HDL led to a reduction in all inflammatory parameters: the leukocyte count decreased by 73%; the neutrophil density decreased by 35%; the IL-6, KC and CCL2 concentration decreased by 4-, 6- and 5-fold respectively. Conclusions: This study shows that HDL may limit the inflammatory process by inhibiting leukocyte recruitment and cytokine release. HDL are likely to represent a mechanism of control of crystal-induced inflammation

Characterization of a specific 20- to 25-kD interleukin-1 inhibitor from cultured human lung macrophages.

Alveolar macrophages have the ability to downregulate immune processes in vitro. We have recently suggested the presence of interleukin-1 (IL-1) inhibitors in the supernatants of human bronchoalveolar lavage cells from patients with idiopathic pulmonary fibrosis or sarcoidosis. In the present study, we further analyze the cellular origin and the biologic properties of a 20- to 25-kD IL-1 inhibitor spontaneously produced by cultured human alveolar macrophages (AM). The inhibitor blocks IL-1-induced prostaglandin E2 production by human fibroblasts and the IL-1-related increase of phytohemagglutinin-induced murine thymocyte proliferation. After rigorous IL-1 alpha and IL-1 beta depletion, supernatants of lung macrophages specifically block the binding of IL-1 to its receptor on the murine thymoma cell line EL4-6.1 in a dose-dependent manner. These results indicate that AM from both normal donors and patients produce a specific IL-1 inhibitor that may be of importance in protecting the alveolar environment from the deleterious effects of excessive IL-1 production

Two-chain structure of the interleukin 1 receptor

AbstractBy crosslinking radioiodinated recombinant human IL1 α to mouse EL4 thymoma cells we have identified in addition to the known IL1-binding proteins of 80 kDa, a second IL1-binding protein of about 40 kDa. This second binding protein could be demonstrated most easily when crosslinking to higher protein complexes was inhibited. This finding suggests that the IL1 receptor, similar to the receptor for other cytokines such as interleukin 2, is composed of a heterodimer, of which both polypeptides contribute to ligand binding

Le projet "SYNAPSY": un point de rencontre entre clinique et neurosciences [The "SYNAPSY" project: where psychiatrists and neuroscientists meet].

The National Center of Competence in Research project "SYNAPSY" aims at identifying certain mechanisms of psychiatric and cognitive disorders, in order to improve the understanding and the genesis of such pathologies, and to promote the development of better diagnostic tools and of new therapeutic approaches. It provides an excellent opportunity for clinical psychiatrists and neuroscientists to develop a synergic mode of collaboration. On the basis of questions stemming from clinical practice and in the frame of patients cohorts, various research projects in neuroscience should lead to progresses that may have a considerable impact on clinical practice