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Biomedical subjects

D R Haynes

Publications and source records attributed to D R Haynes.

48 records · Page 3Linked to original sources
PubMed1991

Interleukin-6 production by human gingival fibroblasts.

The ability of human gingival fibroblasts to synthesize interleukin-6 (IL-6) was studied using in vitro and immunohistochemical techniques. Culture supernatants of human gingival fibroblasts contained significant quantities of IL-6 activity which could be stimulated by fetal calf serum, recombinant interleukin-1 beta and lipopolysaccharide. The activity in the supernatants was specifically attributed to IL-6 since up to 97% of the activity could be inhibited by an anti-IL-6 antibody. Immunohistochemical studies on low-density human gingival fibroblast cultures indicated that the cells were associated with material reactive to the anti-IL-6 antibody. This localization was seen on the cell surface and in the cytoplasm of the cells. Immunoreactivity towards IL-6 was also noted in sections of human gingivae. Moderate staining was seen in the connective tissues and lower portions of the gingival epithelium, while intense staining was seen at foci of inflammation. The identification of IL-6 with human gingival tissues and cells implicates this lymphokine in the molecular events associated with the inflammatory periodontal diseases.

Antibodies↗
PubMed1991

The effects of some anti-arthritic drugs and cytokines on the shape and function of rodent macrophages.

Non-steroidal antiinflammatory drugs (NSAID) enhanced the spreading of mouse and rat peritoneal macrophages attached to either plastic or glass. This was probably due to drug inhibition of prostaglandin E2 (PGE2) production since spreading was also inhibited by adding exogenous PGE2. Corticosteroids (dexamethasone, cortisol and prednisolone) and some immunosuppressants (6-mercaptopurine, methotrexate, but not cyclosporin-A) also enhanced in-vitro spreading of murine peritoneal macrophages. Some recombinant cytokines (human tumour necrosis factor alpha and beta, murine tumour necrosis factor alpha, and murine interferon gamma, but not human interferon gamma) also enhanced the spreading of mouse peritoneal macrophages in vitro. Scanning electron microscopy revealed significant differences in morphology of cells induced to spread by these drugs and cytokines. NSAID treatment also enhanced macrophage clumping in vitro, indicating that cell spreading may play an important role in the resolution of inflammatory processes and/or the formation of multinucleated giant cells.

Adrenal Cortex Hormones↗
PubMed1990

The cyclo-oxygenase inhibitor, piroxicam, enhances cytokine-induced lymphocyte proliferation in vitro and in vivo.

The effects of Piroxicam on the production and activity of lymphoproliferative cytokines (LC) produced by mononuclear phagocytes (MNP) were examined. In vitro, Piroxicam did not affect IL-1 induced thymocyte proliferation (LAF assay). However, the LAF activity from lipopolysaccharide (LPS)-treated MNP cultures was increased after Piroxicam (0.1-20 mumol/L) treatment. The increase in apparent LC activity was largely due to suppression of prostaglandin E2 (PGE2) production. Peripheral blood, spleen and thymus lymphocytes from animals predosed with Piroxicam (5 mg/kg per day for 3 days) synthesized more DNA than untreated mice (as measured by [3H]-thymidine uptake ex vivo). MNP from Piroxicam-treated animals produced significantly more LC. Piroxicam had similar effects in both inflamed and non-inflamed mice. Piroxicam and other non-steroidal anti-inflammatory drugs (NSAID) may therefore stimulate or modulate the immune functions requiring lymphoproliferation by suppressing the formation of PGE2, a natural inhibitor of both LC production and LC-induced lymphoproliferation.

Animals↗
PubMed1990

Prevention of adjuvant-induced cachexia in rats by cyclosporin A.

The changes in food intake and biochemistry following Freund's adjuvant (AJ)-induced inflammation in rats were investigated. Injection of AJ into rats resulted in a transient anorexia but a sustained decrease in body weight. Within 14 days, body weight decreased by 12% (P less than 0.05) and adipose tissue (retroperitoneal fat pads) decreased by more than 50%. Biochemical changes seen in association with the AJ-induced wasting included decreased plasma concentrations of triglyceride and cholesterol. Injection of cyclosporin-A (CS) (20 mg/kg) with the AJ decreased the anorexia, prevented the sustained loss of body weight and adipose tissue and reversed the effects on plasma triglyceride and cholesterol concentrations. Insulin concentrations were not significantly affected by the AJ or AJ/CS treatments. Peritoneal macrophages from AJ-treated rats produced 3-fold more tumour necrosis factor-alpha (cachectin) than control rats. This effect was not observed in rats treated with AJ plus CS. The results are consistent with CS preventing the release of cytokines which have anorectic and catabolic actions (IL-1, TNF), although there is also the possibility that CS has effects involving endocrine mechanisms.

Adipose Tissue↗
PubMed1990

Studies of chemotactic, chemotactic movement-inhibiting and random movement-inhibiting effects of interleukin-1 alpha and beta, tumour necrosis factors alpha and beta and interferon gamma on human neutrophils in assays using 'sparse-pore' polycarbonate (Nuclepore) membranes in the Boyden chamber.

Interleukin-1 alpha and beta (IL-1 alpha and beta), tumour necrosis factors alpha and beta (TNF alpha and beta) and interferon gamma (IFN gamma) were tested for their chemotactic effects, their effects on chemotactic movement towards N-formyl-methionyl-leucyl-phenylalanine (FMLP) and their effects on random locomotion of human peripheral blood neutrophils through polycarbonate membranes in Boyden-type chambers. Both IL-1 alpha and beta, but no other cytokine tested were chemotactic for neutrophils using 'sparse-pore' polycarbonate membrane. Both TNFs, but no other cytokine, inhibited neutrophil chemotactic movement towards FMLP using the same membrane. No cytokine influenced random migration of neutrophils through polycarbonate membrane of standard pore density. These results suggest that IL-1 may have a role as a chemotactic mediator of inflammation, but that TNFs may inhibit chemotactic migration of neutrophils into inflammatory lesions.

Biological Factors↗
PubMed1989

Effect of mitogen and lymphokine stimulation on proteoglycan synthesis by lymphocytes.

The ability of mouse thymocytes and peripheral blood lymphocytes from rats to synthesize and secrete proteoglycans in the presence of a variety of mitogens and lymphokines was studied in vitro, and it was confirmed that such lymphocytes synthesize and secrete significant quantities of proteoglycans. Mitogenic stimulation of the cells with phytohaemagglutanin (PHA) induced a fourfold increase in proteoglycan synthesis; stimulation with interleukin-1 stimulated proteoglycan synthesis up to fivefold. Proteoglycan synthesis could also be stimulated by culturing the cells in the presence of interleukin-2. To determine if this response was related to cell proliferation, the cells were cultured in the presence of PHA and either cyclosporine or prostaglandin E2, two agents that inhibit lymphocyte proliferation. Under these conditions, proteoglycan synthesis remained elevated, indicating that this effect may be independent of cell proliferation. Chemical analysis of the proteoglycans indicated them to be composed of chondroitin sulfate and heparan sulfate. Their molecular size was small compared with cartilage proteoglycans but similar to the small dermatan sulfate proteoglycans synthesized by fibroblasts. On the basis of molecular size, three proteoglycan population were identified, and their relative proportions were altered by mitogenic stimulation of the cells. Taken together, these findings imply that proteoglycan synthesis is intimately associated with lymphocyte activation and may be related to cellular function in immune responses.

Animals↗
PubMed1989

Interleukin 2 and interleukin 2 inhibitors in human serum and synovial fluid. I. Characterization of the inhibitor and its mechanism of action.

An inhibitor of the murine interleukin 2 (IL-2) dependent cell line (CTLL-2) has been demonstrated in sera from healthy subjects as well as in sera and synovial fluid from patients with inflammatory arthritides. This inhibitor inhibits the mitogenic response of normal peripheral blood mononuclear cells and seems to be primarily due to impaired IL-2 production. The inhibitor does not appear to bind to IL-2 or the IL-2 receptor. This inhibition can be reversed with IL-2 but not interleukin 1. These observations may apply to the defects in IL-2 production and response demonstrable in rheumatoid arthritis and other autoimmune disorders.

Adult↗
PubMed1988

Effect of gold salt treatment on the receptor binding activity of monocytes and macrophages isolated from rats with adjuvant arthritis.

We investigated the effect of chrysotherapy on the Fc and complement receptor binding activity of peripheral blood (PB) monocytes and peritoneal (PE) macrophages isolated from normal rats and rats with adjuvant induced arthritis. The adjuvant induced severe disease in Dark Agouti (DA) rats and less marked disease in J. C. Lewis (JC) rats. Gold treatment reduced the disease in DA rats but exacerbated the disease in JC rats. PB monocytes generally exhibited increased receptor activity after adjuvant injection. Gold treatment resulted in a simultaneous reduction of the PB monocyte receptor activity and increased the PE macrophage receptor activity. This was considered to be due to a direct effect of gold, since the Fc receptor activity of PE macrophages increased after in vitro gold treatment.

Animals↗
PubMed1988

Do gold drugs inhibit interleukin-1? Evidence from an in vitro lymphocyte activating factor assay.

The ability of some antiarthritic gold (I) compounds to inhibit the in vitro lympho-proliferative activity of human interleukin-1 (IL-1) in the lymphocyte activating factor (LAF) assay was investigated. Marked inhibition was seen at concentrations of auranofin (AF) and gold sodium thiomalate (GSTM) that correspond to gold levels found in the serum of patients receiving these drugs. This inhibition was not due to direct inactivation of the IL-1 molecule. Omitting 2-mercaptoethanol from the LAF assay potentiated the effect of GSTM. The antiproliferative effect of AF occurs almost immediately and probably reflects its direct cytotoxicity to stimulated lymphocytes.

Animals↗