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S J Hopkins

Publications and source records attributed to S J Hopkins.

At least 55 records · Page 3Linked to original sources

Contact hypersensitivity induces plasma interleukin 6.

Previous studies in this laboratory have revealed that elicitation reactions in contact-sensitized mice correlate closely with elevations in the serum concentration of acute-phase proteins. Regulation of the hepatic synthesis of acute-phase proteins is one of the many biological functions ascribed to interleukin 6 (IL-6). We now provide evidence that contact reactions are also associated with a rapid and substantial increase in the plasma concentration of IL-6. Quantitative assessment of plasma IL-6 may provide a useful serological method for the evaluation of experimental allergic contact dermatitis in mice, and possibly in other species.

Animals↗

Production of interleukin-1 by draining lymph node cells during the induction phase of contact sensitization in mice.

Biologically active interleukin-1 (IL-1) has been detected in supernatants of draining lymph node cells isolated from contact-sensitized mice. Induction of IL-1 was dependent upon the concentration of sensitizer applied and occurred within 2 hr of exposure. The IL-1 activity could not be attributed to other interleukins and was neutralized by a specific antiserum. Reduced concentrations of IL-1 were produced by cells isolated from the draining nodes of mice that had been pre-exposed to the sensitizer. Since IL-1 has the potential to influence several aspects of lymphocyte activation, the production of significant concentrations of biologically active IL-1 by draining lymph node cells indicates that it is likely to play an important role in the afferent phase of contact sensitization.

Animals↗

Simple, sensitive and specific bioassay of interleukin-1.

This paper describes a convenient method for the culture of sub-lines of the murine T cell cloned line, D10.G4.1, and the use of these lines in a highly sensitive and specific bioassay for interleukin-1 (IL-1). The cells are cultured with IL-1, interleukin-2 (IL-2), and concanavalin A (ConA), in the absence of feeder cells or antigen. Assays are routinely carried out in the presence of saturating IL-2, which enhances sensitivity and ensures that further IL-2 will not give false positives. Addition of interleukin-4 (IL-4) has a similar effect and can be used together with IL-2 where there is a potential for interference from either cytokine. The assay is not affected by high concentrations of human interleukin-6 or tumour necrosis factor-alpha (TNF-alpha) and only minimally affected by high concentrations of murine TNF-alpha.

Animals↗

Cytokines in synovial fluid: II. The presence of tumour necrosis factor and interferon.

Cytokine-specific monoclonal antibodies were used in enzyme-linked immunoadsorbant assays (ELISA) to examine a variety of synovial fluids for the presence of cytokines which might be expected to play some part in the pathology of arthritis. Low, but significant, levels of tumour necrosis factor alpha (TNF-alpha) were present in the majority of synovial fluids obtained from rheumatoid arthritis patients with a sero-positive history. Low levels of interferon (IFN)-alpha and IFN-gamma were also detected, but only IFN-alpha was significantly increased in the sero-positive group. Tumour necrosis factor beta (TNF-beta) was present only in trace amounts. These results suggest that the presence of cytokines, such as TNF-alpha and IFN-alpha in synovial fluid may be associated with tissue changes observed in rheumatoid joint disease and thus contribute to the pathology of the arthritis, but support evidence for the minimal role likely to be played by IFN-gamma in the joint pathology of rheumatoid arthritis.

Arthritis↗

Cytokines in synovial fluid. I. The presence of biologically active and immunoreactive IL-1.

Using a sensitive IL-1-dependent T cell clone we estimated interleukin 1 (IL-1)-like activity in a variety of synovial fluids (SF). Although we demonstrate that SF contains potent inhibitors of endogenous and exogenous IL-1 we were able to estimate that samples from rheumatoid arthritis, osteoarthritis and other arthritides contain the equivalent of tens or hundreds of picograms of IL-1 per millilitre, when compared to a standard IL-1 preparation. Although there was some correlation between these results and those obtained using a radio-immunoassay (RIA) for IL-1 beta, the RIA indicated that IL-1 was present in the nanogram range. The results suggest that the importance of inhibitors of IL-1 in SF merits particular attention and that it is also important to consider the bioactivity of cytokines which may be detected by physical methods.

Arthritis↗

B-cell-derived interleukin 1 (IL-1)-like factor. I. Relationship of production of IL-1-like factor to accessory cell function of Epstein-Barr virus-transformed human B-lymphoblast lines.

The relationship of production of interleukin 1 (IL-1)-like factor to accessory function of Epstein-Barr virus (EBV)-transformed B lymphocytes was examined. Six of eight human EBV-B cell lines spontaneously produced and released detectable levels of thymocyte comitogenic factor in vitro, but no interleukin 2 (IL-2) activity. Eight of eight produced fibroblast proliferation activity. Culture supernatants from the two apparent nonproducers of thymocyte comitogenic activity induced the proliferation of the IL-1-dependent murine helper-T-cell clone D10G4.1 in the presence of concanavalin A (Con A). One of the EBV-B cell lines produced a potent inhibitory factor in addition to IL-1-like thymocyte comitogenic and fibroblast proliferation factors. The inhibitory factor inhibited mouse thymocyte proliferative response to Con A, and the proliferation of the IL-2-dependent CT6 cell line, but not human fibroblast growth. All but one of the eight EBV-B cell lines tested, the exception being the line that produced an inhibitory factor, were able to serve as antigen-presenting cells that enabled purified human T lymphocytes to proliferate in one-way mixed lymphocyte reactions (MLR) and in response to Con A. The supernatants of 14 of 16 clones derived from two of the EBV-B cell line cells contained thymocyte comitogenic activity and all 16 stimulated fibroblast proliferation. The phenotypic characteristics of the EBV-B cell lines were heterogeneous, but there was no clear-cut relationship between the cell surface phenotypes of either the cloned or uncloned EBV-B cells and their ability to produce these factors. These studies show that all of the EBV-B cell lines that can function as accessory cells have the capacity to produce an IL-1-like factor.

Animals↗

Characterization of the IgG antibody response to timothy grass pollen antigens.

The IgG and IgE antibody responses against timothy grass pollen antigen B (AgB) in several mouse strains were determined. Considerable variability in both responses was demonstrated, and (CBA/J X C57BL/6)F1 mice were selected for use in subsequent experiments. Anti-idiotypic-antibody-induced T suppressor cells almost completely suppressed AgB-specific IgE, but the IgG response was not altered. Further studies with photooxidized AgB (Ox-AgB) indicated that the IgG response was directed against an antigenic determinant expressed on both native antigen and Ox-AgB. Our data indicates that AgB possesses two distinct antigenic determinants, one that induces an IgE response, and one that induces an IgG response.

Animals↗

Pristane-induced arthritis in Balb/c mice. I. Clinical and histological features of the arthropathy.

Intraperitoneal injection of pristane induced a clinical peripheral arthritis and/or tenosynovitis in 40% of 40 Balb/cJ/Ola mice. Hind paws were always affected first and fore paws were frequently involved. Involvement of knee joints was only apparent histologically. Some clinically unaffected animals and apparently uninvolved joints from arthritic mice were also shown to have a synovitis histologically. The time of onset and pattern of arthritis was variable. The development of arthritis was not related to plasmacytoma or ascites induction, which occurred in a similar percentage of mice over a similar period. The earliest change was synoviocyte hyperplasia and polymorphonuclear infiltration in the subintima. There was no obvious mononuclear cell infiltration. In the later stages there was erosion of cartilage and sclerosis of underlying bone. These features resemble the joint changes seen in osteoarthritis.

Animals↗

Inhibition of lymphocyte activation by gold sodium thiomalate.

Activation of lymphoid cells by both T and B cell mitogens was inhibited by gold sodium thiomalate (GST). The action of GST did not appear to be exerted at early stages of lymphocyte activation. Inhibition by GST was sustained throughout 4 days of culture. The inhibitory effect of GST was reduced at low serum concentrations. Sodium thiomalate and sodium chloroaurate were also able to inhibit lymphocyte activation.

Animals↗

Captopril.

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Captopril↗

Tiaprofenic acid.

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Anti-Inflammatory Agents↗

Triazolam.

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Anti-Anxiety Agents↗

Piperacillin.

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Adult↗