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Biomedical subjects

P Miossec

Publications and source records attributed to P Miossec.

At least 127 records · Page 7Linked to original sources

Inhibitor of interleukin-2 in rheumatoid synovial fluid.

Although large numbers of T cells infiltrate the synovium of patients with rheumatoid arthritis (RA), the responses of these cells, as present in the blood and synovial fluid (SF), to exogenous interleukin-2 (IL-2) and their production of IL-2 are diminished. To investigate this functional defect, RA SF were examined for the presence of inhibitors of IL-1 and IL-2. A factor was found which inhibited the IL-2-induced proliferation of mitogen-stimulated human T cells and the IL-1-induced proliferation of C3H/Hej mouse thymocytes, but not IL-1-induced fibroblast proliferation. On AcA 54 Ultrogel filtration, the inhibitory activity resided in a fraction with an apparent molecular weight of greater than 70 kd and a major pI of 6.8. The inhibitory effect of RA SF on lymphocyte proliferation was partially corrected with IL-2, but not with IL-1. In the presence of RA SF, normal lymphocytes showed not only a decreased response to exogenous IL-2, but also a decreased production of IL-2. The presence of an inhibitor of IL-2 in RA SF could contribute to the IL-2-related T cell defects observed in RA.

Animals↗

Inhibitor of interleukin-2 synthesis and response in rheumatoid synovial fluid.

We studied the effects of a factor present in rheumatoid arthritis (RA) synovial fluid (SF) on interleukin-2 (IL-2)-dependent cell proliferation and on the production of IL-2 by mitogen-stimulated peripheral blood mononuclear cells. RA SF suppressed the responsiveness of a mouse T cell line (HT-2) to IL-2, indicating that it contained an inhibitor of the IL-2 response. When RA SF was fractionated by Sephadex G-200 gel filtration, the inhibitory activity was detected mainly in fractions with a molecular weight of approximately 150,000, but was also found in a 15-19-kd fraction. Removal of IgG from the 150-kd fraction, by means of an anti-IgG affinity column, did not reduce the activity of the fraction, nor was activity found in the eluted IgG. The inhibitory fractions reduced mouse thymocyte proliferative responses to IL-1 in the presence of phytohemagglutinin, and reduced the production of IL-2 by human peripheral blood mononuclear cells, but did not inhibit IL-1-induced human foreskin fibroblast proliferation; this suggests that the factor was not an IL-1 inhibitor. The inhibitory activity of the RA SF factor was blocked by an antibody against an inhibitor of IL-2 that was purified from a culture of the human monocytic leukemia cell line, THP-1. This finding also supports the conclusion that RA SF contains an IL-2 inhibitory factor. The observed inhibition of both IL-2 synthesis and IL-2 response suggests that the target of the inhibition was the T lymphocyte.

Animals↗

Pathways to chronic inflammation in rheumatoid synovitis.

Postcapillary venules resembling the high endothelial venules (HEVs) of lymphoid tissues have often been observed at sites of chronic inflammation. We have therefore postulated that such venules may be an important site of lymphocyte migration into rheumatoid synovial membrane and that inflammatory cell products may act on endothelial cells (ECs) to increase lymphocyte emigration. Electron microscopic examination of rheumatoid synovial membranes showed that a strong correlation existed between the proportion of lymphocytes in perivascular tissue and the height/base ratio of the ECs in those areas. In addition, binding experiments showed that peripheral blood mononuclear cells preferentially bound to ECs in sections of rheumatoid synovial membrane that had the morphological appearance of HEVs. In vitro binding experiments, in which lymphocyte adhesion to human umbilical vein EC monolayers was measured, showed that adhesion was enhanced by preincubation of the ECs with interferon-gamma or interleukin 1 (IL 1). The central role of IL 1 in increasing lymphocyte migration into the rheumatoid synovial membrane was also supported by the findings that IL 1 is chemotactic for lymphocytes, ECs can secrete IL 1, and IL 1 activity is readily detectable in synovial fluids of rheumatoid arthritis patients.

Arthritis, Rheumatoid↗

Acute synovial fluid eosinophilia associated with delayed pressure urticaria: a role for mast cells?

We report a case of exercise induced joint effusion with synovial fluid (SF) eosinophilia of 9,540/mm3 in a patient with delayed pressure urticaria. The SF eosinophilia was an acute but transient event associated with some evidence of local complement activation. Histologic assessment revealed a normal synovial membrane but with no detectable intact mast cells. These observations suggest that mast cells and eosinophils acting in concert can cause joint inflammation.

Acute Disease↗

Immune interferon enhances the production of interleukin 1 by human endothelial cells stimulated with lipopolysaccharide.

Interferon-gamma (IFN-gamma) is a macrophage-activating factor that has also been shown to act on endothelial cells (EC). Interleukin 1 (IL 1), first described as a monocyte product, is also produced by EC after stimulation by lipopolysaccharide (LPS). In this study, the effect of IFN-gamma on the release of IL 1 by EC stimulated with LPS has been investigated. Although IFN-gamma did not stimulate the release of IL 1 or increase the apparent intracellular pool of IL 1 when incubated with EC, there was an increase in the amount of IL 1 released when cells preincubated with IFN-gamma were stimulated with LPS. The effect of IFN-gamma increased with concentration (1 to 1000 U/ml) and with duration of preincubation (24 to 96 hr). The presence of IFN-gamma was not required during the stimulation with LPS. When EC were cultured without IFN-gamma for increasing time periods up to 96 hr, the amount of IL 1 released by EC on subsequent stimulation with LPS progressively decreased. Addition of as little as 1 U/ml of IFN-gamma, however, prevented the loss in capacity of EC to secrete IL 1 when stimulated with LPS. In vivo, EC are involved in the emigration of mononuclear cells from the blood to inflammatory sites. Because IL 1 is chemotactic for lymphocytes and also increases the binding of lymphocytes to EC, activation of EC by T cell-derived factors such as IFN-gamma may augment lymphocyte emigration by increasing the release of IL 1 at the blood-tissue interface.

Cells, Cultured↗

Production of interleukin 1 by human endothelial cells.

Vascular endothelial cells (EC) play an important role in the emigration from the blood of the mononuclear cells that participate in the chronic inflammatory response. Because EC express a number of functions of cells of the monocyte/macrophage lineage, EC culture supernatants (ECSN) were examined for the presence of IL 1. In these supernatants, IL 1 activity was low when EC were cultured in the presence of serum. The low level of activity appeared to be due to the spontaneous production by the EC of inhibitors of the thymocyte proliferation assay of IL 1, of 70 kd and 9 kd, as measured by AcA Ultrogel filtration. When EC were cultured in the absence of serum, IL 1 activity was easily demonstrated in crude supernatants. Upon stimulation with LPS, the amounts of IL 1 activity were greatly increased. The release of IL 1 was an early event, detectable after 1 hr of incubation and reaching a maximum after 24 hr. The IL 1 activity produced by EC demonstrated a number of similarities to that of IL 1 produced by monocytes. On AcA 54 gel filtration, as with monocyte-derived IL 1, the IL 1 activity was found in two peaks of 50 to 60 kd and 16 to 18 kd. Upon chromatofocusing of the 16 to 18 kd peak, three active fractions were found, eluting near pH 7.0, 5.6, and 5.0. In addition, when LPS-stimulated ECSN and purified monocyte-derived IL 1 were incubated with a rabbit anti-IL 1 antibody, a parallel reduction in thymocyte-stimulating activity was observed, suggesting that the active agent in ECSN shared a common antigenic site with IL 1. The demonstration of IL 1 production by EC provides additional evidence that these cells, in addition to their functions as vascular cells, may also participate in some of the immune and nonimmune functions previously ascribed to macrophages.

Antibodies↗

Interleukin-1 lymphocyte chemotactic activity in rheumatoid arthritis synovial fluid.

We examined the role of interleukin-1 (IL-1) in the chemotactic activity of rheumatoid arthritis (RA) synovial fluid (SF). Crude RA SF was found to be chemotactic for B cells and T cells. After AcA 54 gel filtration, the principal peaks of chemotactic activity were found in the 5-kd, 16-kd, and 60-kd fractions. The majority of the chemotactic activity for both the B cells (74-85%) and the T cells (69-78%) was removed from these fractions by treatment with anti-IL-1 antibody. However, in crude SF, approximately 60% of the chemotactic activity for B cells and 40% of that for T cells was removed, indicating the presence of additional chemotactic factors in RA SF. IL-1 activity, measured by the thymocyte proliferation assay, was demonstrated in RA SF AcA 54 Ultrogel fractions after separation from inhibitors of thymocyte proliferation that are present in crude SF. On chromatofocusing of the 16-kd fraction, the principal peaks of both thymocyte proliferation activity and chemotactic activity were present in the same fractions with pI values of 6.8, 5.7, and 5.2, which are characteristic of IL-1. The demonstration of IL-1-associated chemotactic activity in RA SF may reflect the presence in the RA synovial membrane (including both the lining layer and the subsynovial layer) of activated macrophages, interstitial histiocytic cells, and other IL-1-producing cells, such as endothelial cells. These findings suggest that such cells may attract lymphocytes to their environment by secretion of IL-1.

Arthritis, Rheumatoid↗

Lowered Fc IgG receptor-bearing T lymphocytes correlate with non-organ-specific autoantibodies in silicosis.

A survey of silicosis patients and people exposed to silica dust was set up in an effort to look for any relationship between humoral and cell-mediated autoimmune phenomena. It was found that in both sets of subjects, the level of Fc IgG receptor-bearing T lymphocytes was significantly reduced, there was also an inverse correlation between these cell concentrations and IgG- and IgM-circulating immune complex levels. In addition, raised levels of various autoantibodies were found in both groups, however, none of the exposed subjects has developed silicosis to date.

Adolescent↗

[Serological profile in so-called seronegative rheumatoid arthritis].

89 cases of sero-negative rheumatoid arthritis (RA) were compared to 127 cases of sero-positive RA. Anti-perinuclear and anti-keratin antibodies were detected less frequently in the first group (51 vs 67% and 28 vs 33%, respectively), while the inverse was found for anti-nuclear antibodies (28 vs 24%). "Light" rheumatoid factors (RF)--IgG, IgM, IgE, IgA and IgD--were detected in 23.6, 21.3, 17.5, 11.3 and 0 per cent of cases of sero-negative R.A. The evolutive state of these cases was less severe. RF agglutinins were detected in 5 out of 12 samples of synovial fluid tested in cases of sero-negative RA.

Adult↗

Lymphocyte chemotactic activity of human interleukin 1.

In the cellular immune response, there is an accumulation of mainly nonantigen-specific mononuclear cells that presumably is dependent on the local secretion of chemotactic factors. In view of the presence of large numbers of macrophages early in the delayed hypersensitivity response, the possible role of these cells in the chemotaxis of lymphocytes was investigated by studying the chemotactic activity of purified human interleukin 1 (IL 1) on T and B cells. Chemotactic activity for T and B cells was observed, the effect on B cells being greater than on T cells. At low concentrations (less than 1 U/ml), IL 1 had predominantly chemotactic activity for B cells and chemokinetic activity for T cells. At high concentrations (10 to 20 U/ml), IL 1 had pure chemotactic activity for both cell types. A relationship was found between levels of migration of T and B cells and mouse thymocyte proliferation induced by purified IL 1 and by lipopolysaccharide-stimulated monocyte supernatants. The principal peaks of both activities were found in 16,000 to 18,000 m.w. fractions. In additional studies, the chemotactic response to IL 1 was inhibited by preincubation of T and B cells with IL 1 or stimulated monocyte supernatant, demonstrating the role of binding of IL 1 in the chemotactic response.

Animals↗

[Significance of antinuclear anti-histone antibodies].

The results of routine antihistone antibody (AHA) assay in a preliminary series of 189 sera are presented. There were 23 positive tests (systemic lupus erythematosus, 8 cases; drug induced SLE, 4 cases; rheumatoid arthritis 7 cases; and multiple sclerosis, 1 case; chronic active hepatitis, 1 case; systemic sclerosis, 1 case and primary biliary cirrhosis 1 case). The results of routine assay in 5 other patients groups are reported: 30 spontaneous SLE (9 positive AHA), 63 rheumatoid arthritis (2 positive AHA), 19 Sjögren syndrome (no AHA), 11 primary biliary cirrhosis (1 positive AHA) and 7 mixed connective tissue disease (no AHA).

Adolescent↗

[Serum immunoglobulins and complement fractions in protein malnutrition].

Serum immunoglobulins and some complement components (C1q, C3c, C4, factor B, C9) have been evaluated in 99 malnourished patients. The sole abnormality which seems related to protein calorie malnutrition is a C1q decrease significantly correlated to serum albumin, thyroxin binding prealbumin and retinol binding protein. The immunoglobulins modifications seem to be related to pathological conditions associated with malnutrition (sepsis, liver diseases).

Adult↗

[Influence of the localization on the prognostic value of E, E-active and autologous rosettes in lung, esophagus and otorhinolaryngologic cancer].

E, E-active and autologous-rosette-forming-lymphocytes (E, Eact-, auto-RFC) were studied in 66 patients with lung cancer (2 stage I, 17 stage II, 20 stage III, 27 stage IV), 42 patients with head and neck cancer (14 stage III, 28 stage IV) and 22 patients with esophagus cancer (11 stage II, 6 stage III, 5 stage IV). Compared to controls, E-RFC were found to be depressed in each of the three different localizations (p less than 0.001), Eact-RFC were found to be depressed in head and neck as well as esophagus cancer (p less than 0,05 and p less than 0,01 respectively) and auto-RFC were found to be depressed in lung and esophagus cancer (p less than 0,01). Mean survival times of patients with RFC over and under 1 SD below the average value were compared. Significant differences were demonstrated in E-RFC and auto-RFC for head and neck cancer and in Eact-RFC for lung cancer.

Adult↗

[Antiperinuclear and antikeratin antibodies in liver diseases].

Antiperinuclear factor (APF) was detected in 7 out of 38 patients with autoimmune liver disease (AILD) and in 7 out of 83 patients with non-autoimmune liver disease (NAILD). Anti-keratin antibodies were found in 2 out of 18 patients with AILD and in 3 out of 32 patients with NAILD. Neither APF nor antikeratin antibody was significantly more frequent in AILD than in NAILD. The incidence of APF was shown to be greater (p less than 0.02) in patients with rheumatoid factor (RF) and/or antinuclear antibody. This supports the hypothesis that APF is connected with RF rather than with rheumatoid arthritis, although the presence of APF is evidence towards the diagnosis of rheumatoid arthritis.

Adult↗

Low-affinity E-rosette-blocking factor in hemodialysis-treated patients in chronic renal failure.

Enumeration of total E-rosette-forming cells (t-ERFC) enabled 30 renal failure patients on hemodialysis to be classified into three groups: group 1 with normal numbers of t-ERFC, and groups 2A and 2B with reversibly and irreversibly reduced numbers, respectively. Duration of dialysis treatment was the only distinguishing feature between these three groups, being shorter for group 1 than for group 2A (P less than 0.02) and shorter for group 2A than for group 2B (P less than 0.001). However, a rosette-blocking factor (RBF) was demonstrated in all three groups which predominantly affected the low-affinity ERFC (i.e., total ERFC minus active ERFC). This factor could be partially absorbed (P less than 0.01) on normal lymphocytes and showed increased activity after a single dialysis session, suggesting the removal by dialysis of a putative anti-RBF substance.

ABO Blood-Group System↗

A study of familial lupus erythematosus-like disease and hereditary angio-oedema treated with danazol.

Immunological and genetic studies were performed in a family in which the mother and five siblings had hereditary angio-oedema (HAE). LE cells, antinuclear factors, antibodies to double-stranded DNA and positive direct Coombs' test were not found in any of the subjects. One female sibling had a lupus erythematosus-like illness with skin lesions of the face which responded to danazol treatment. Laboratory evidence of HAE was obtained in the entire kindred and all the siblings shared HLA haplotype AIB7 inherited from the deceased mother.

Adolescent↗