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At least 307 records · Page 17Linked to original sources

PubMed1992

Fuscoside: an anti-inflammatory marine natural product which selectively inhibits 5-lipoxygenase. Part I: Physiological and biochemical studies in murine inflammatory models.

The biological and biochemical pharmacology of fuscoside, a novel anti-inflammatory marine natural product isolated from the Caribbean gorgonian Eunicea fusca, has recently been characterized using murine (part I) and human (part II) models of inflammation. Topically applied fuscoside (FSD) effectively inhibits phorbol myristate acetate (PMA)-induced edema in mouse ears at levels comparable with indomethacin over a 3.3-hr exposure period, and is significantly more efficacious than indomethacin over 24 hr in the PMA model. Histological preparations and quantification of the neutrophil-specific marker, myeloperoxidase, demonstrate that FSD inhibits neutrophil infiltration into PMA-induced regions of edema and inflammation. In systemic studies, where FSD is injected i.p. before the topical application of PMA, negligible effects on ear inflammation are observed. FSD does not inhibit bee venom or human synovial fluid phospholipase A2 up to concentrations of 500 microM. In calcium ionophore-activated cultures of mouse peritoneal macrophages, FSD selectively and irreversibly inhibits leukotriene C4 biosynthesis (IC50 = 8 microM), yet has negligible effects on prostaglandin E2 production. FSD is also without effect on the conversion of arachidonic acid to prostaglandin E2 by ram seminal vesicle cyclooxygenase. Chromatographic and spectroscopic studies suggest that FSD is not metabolized, and that drug uptake/binding by macrophages is time dependent, saturable and independent of active transport mechanisms. These studies represent the first report of an anti-inflammatory marine natural product that selectively inhibits leukotriene biosynthesis.

Animals↗

PubMed1996

Non-steroidal anti-inflammatory agents, Part 20. Method for testing non-steroidal anti-inflammatories: the modified hen's egg chorioallantoic membrane test (HET-CAM test) compared to other procedures.

The delay of onset of irritation phenomena at the chorioallantoic membrane of incubated hen's eggs, a parameter for anti-inflammatory activity, was determined for the pharmaceutical substances diclofenac, flufenamic acid, ibuprofen, indomethacin, ketoprofen, piroxicam, phenylbutazone, salicylic acid, and sodium salicylate. Alongside questions relating to the dose-effect ratio, metabolisation, recovery, and diffusion of the substances to their site of action were investigated. The reproducibility of the procedure and its selectivity with regard to substances with a different mechanism of action is proven. The method allows classification of the substances according to their anti-inflammatory potency. However, correlation with the results of enzyme inhibition or in vivo results is only possible to a limited extent.

Animals↗

PubMed1999

Comparison of suppressive effects of a new anti-inflammatory compound, FR167653, on production of PGE2 and inflammatory cytokines, human monocytes, and alveolar macrophages in response to endotoxin.

FR167653 [1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1,2,4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate] was developed to inhibit proinflammatory cytokine production. However, the effects of FR167653 on prostanoid production are unclear. We investigated the effect of FR167653 on proinflammatory cytokine and prostaglandin (PG) production by lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes and alveolar macrophages (AM) from the same individuals, and compared the effects in monocytes and AM. FR167653 inhibited interleukin-1beta and tumor necrosis factor alpha production. The effect on PGE2 production was assessed by four parameters. FR167653 inhibited PGE2 synthesis and LPS induction of cyclooxygenase activity. Western and Northern blot analyses revealed that LPS induction of cyclooxygenase-2 expression was attenuated by this compound. The suppression in monocytes was greater than that in AM. We concluded that the reduction of LPS-induced PGE2 synthesis by FR167653 was due to inhibition of cyclooxygenase-2 production. These results show that FR167653 may be therapeutically useful for inhibiting production of both inflammatory cytokines and PG production in inflammatory diseases.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1996

Reciprocal effects of pro-inflammatory stimuli and anti-inflammatory drugs on the activity of heat shock factor-1 in human monocytes.

Heat shock factor-1 (HSF-1), the transcriptional activator of heat shock genes has recently been shown to play a role in the repression of acute phase genes. We have further explored the role of HSF-1 in inflammatory processes in human monocytes. HSF-1 was activated in these cells by a wide range of classes of non-steroidal antiinflammatory drugs (NSAIDs) while being strongly repressed by pro-inflammatory stimuli. The experiments indicate reciprocal regulation of the acute phase and heat shock responses and suggest a novel target for the NSAID family of drugs.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1993

In vivo anti inflammatory effects of the M20 IL-1 inhibitor: I. Effects on acute inflammatory parameters.

Previous studies have described an IL-1 Inhibitor produced by a myelomonocytic line developed in our laboratory (Eur J Immunol 1986; 16: 1449). This IL-1 Inhibitor was secreted by the M20 line constitutively in addition to IL-1, from which it could be separated. We have recently shown that the M20 IL-1 Inhibitor is distinct from the IL-1ra. In vitro this factor inhibited IL-1 induced proliferative responses as well as PGE2 secretion by IL-1 induced fibroblasts. We also showed for the first time (Lymphokine Research 1988; 7(3): 268) that an IL-1 inhibitor can reduce IL-1 induced inflammatory effects. This study describes the specific effect of the M20 IL-1 Inhibitor on IL-1 induced parameters of inflammation: fever, leukocytosis and local foot pad swelling or lymph node enlargement. Purified preparations of the IL-1 Inhibitor, when injected together with IL-1, or before the IL-1, reduced fever, leukocytosis, foot pad swelling and lymph node enlargement caused by IL-1. Similar responses were obtained by injection of IL-6 or TNF, but were unaffected by the IL-1 Inhibitor, when injected together. These results indicate that the M20 IL-1 Inhibitor acts specifically on IL-1 induced responses in vivo. The potential importance of this factor as an anti-inflammatory and immune regulatory factor, is supported by the findings of this study.

Animals↗

PubMed1979

Inflammatory response linked to oxazolone-indued cutaneous basophil hypersensitivity: effect of different immunomodulator and anti-inflammatory drugs.

The potency of cytostatic and anti-inflammatory drugs was tested on the oxazolone-induced cutaneous basophil hypersensitivity (CBH) in mice. The challenge reaction was performed early after sensitization in order to minimize B-cell expression; exudative and cellular infiltration was estimated 6 h, 24 h and 48 h after challenge. The potency of drugs was tested at three different periods of immunization: 2 days before or after sensitization or before challenge. Cytostatics act mainly when cells are being committed, a corticoid acts on inflammation linked to committed cells, NSAIDs show inconstant anti-inflammatory effects on this test. D-Penicillamine and levamisole act in the same depressive profile in normal animals. Thus the CBH model appears to be relevant in studying drug activities on inflammation linked to T-cell expression.

Animals↗

PubMed2006

Macrophage inflammatory protein (MIP)1alpha and MIP1beta differentially regulate release of inflammatory cytokines and generation of tumoricidal monocytes in malignancy.

The C-C chemokines, macrophage inflammatory protein (MIP)1alpha and MIP1beta are potent chemoattractants for the monocytes, which form an important component of the stroma of tumor tissue and may regulate tumor growth and associated inflammation. We examined the role of MIP1alpha and MIP1beta in inducing the release of inflammatory cytokines and the generation of tumoricidal monocytes from the peripheral blood monocytes (PBM) of healthy women and patients with carcinoma of breast (CaBr). Interleukin-1 (IL-1) and tumor necrosis factor (TNF) alpha release by the PBM was markedly stimulated by MIP1alpha in CaBr patients, but only marginally so in healthy women. In contrast, MIP1beta stimulated the release of these cytokines by the PBM of healthy women, but failed to do so in CaBr patients. MIP1alpha, but not MIP1beta, synergized with LPS in inducing the release of IL-1 from the PBM of both healthy women and CaBr patients. Both MIP1alpha and MIP1beta augmented respiratory bursts in PBM and generated tumoricidal PBM that killed T24 cells, MIP1alpha being more effective in CaBr patients and MIP1beta in healthy women. IFN-gamma co-stimulated and IL-4 suppressed MIP1alpha and beta-induced cytotoxicity in PBM. The synergy of IFN-gamma was more marked with MIP1alpha than with MIP1beta. The differential effects of MIP1alpha and MIP1beta on the PBM of healthy women and CaBr patients co-related with the levels of expression of CCR1 and CCR5 in these monocytes. The expression of CCR5 was higher than that of CCR1 in the PBM of healthy women and the PBM of the CaBr patients showed overexpression of CCR1 and downregulation of CCR5.

Adenocarcinoma↗

PubMed2002

The in vitro anti-inflammatory effects of recombinant anti-CD25 immunotoxin on lamina propria T cells of patients with inflammatory bowel disease are not sufficient to cure experimental colitis in mice.

BACKGROUND AND AIMS: In chronic inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis an aberrant mucosal immune regulation is observed accompanied by upregulation of proinflammatory cytokines. Lamina propria T cells of inflamed mucosa have an activated phenotype characterized by increased expression of surface markers such as CD25. We therefore determined the anti-inflammatory effect of a recombinant immunotoxin consisting of an anti-CD25 single chain variable fragment (scFv) fused to a deletion mutant of Pseudomonas exotoxin A [RFT5(scFv)ETA'] on isolated lamina propria lymphocytes of patients with IBD and in the murine model of trinitrobenzene sulfonic acid (TNBS) induced colitis. PATIENTS AND/METHODS: Lamina propria lymphocytes of 25 patients with IBD and 19 control patients were stimulated in absence or presence of RFT5(scFv)ETA'. Interferon-gamma production was determined in the supernatant by ELISA and the induction of apoptosis by flow cytometry after propidium iodide staining. BALB/c mice received TNBS intrarectally and were treated with RFT5(scFv)ETA'. RESULTS: In vitro the administration of RFT5(scFv)ETA' significantly reduced interferon-gamma production and increased apoptosis in lamina propria lymphocytes isolated of inflamed mucosa. However, this contrainflammatory regulation did not result in gain of weight or increased life span in experimental colitis in vivo. CONCLUSION: In addition to the downregulation of the proinflammatory cytokine in vitro, RFT5(scFv)ETA' induced neither a direct nor a bystander effect in an in vivo model of colitis. Therefore our data do not support potential therapeutic implications of targeting CD25 by RFT5(scFv)ETA' in chronic IBD.

Adult↗

PubMed1984

Interstitial nephritis, proteinuria, and renal failure caused by nonsteroidal anti-inflammatory drugs. Immunologic characterization of the inflammatory infiltrate.

Nine patients with the unusual combination of renal failure, nephrotic-range proteinuria, and biopsy-proved interstitial nephritis are described. Six of these patients had received nonsteroidal anti-inflammatory agents (three fenoprofen, one ibuprofen, one zomepirac, and one tolmetin). The remaining three patients had no history of exposure to drugs known to cause interstitial nephritis. Immunologic characterization of the infiltrating cells with monoclonal antibodies showed that the majority of cells in most cases were cytotoxic T cells, although some B cells were present in all cases. Giant collecting duct cells were seen in half the patients with drug exposure but in none of the others. Otherwise, there were no conspicuous morphologic differences between patients with and without drug exposure. Many of the patients had associated glomerular abnormalities. Only the zomepirac and tolmetin recipients showed pure interstitial disease. The three fenoprofen recipients and the zomepirac and tolmetin recipients regained normal renal function after the drug was discontinued. The combination of renal failure, nephrotic range proteinuria, and interstitial nephritis is one form of nephrotoxicity observed in patients treated with nonsteroidal anti-inflammatory agents. However, this lesion, which may be mediated by cytotoxic T cells, may also be seen rarely in patients with no apparent drug exposure.

Adult↗

PubMed1982

Non-steroidal anti-inflammatories--XII. Mode of action of anti-inflammatory methane sulfonanilides.

The influence of anti-inflammatory methane sulfonanilides on the arachidonic acid metabolism in ram seminal vesicle homogenate depends on the pK3 of the individual substance: more acidic compounds suppress, less acidic compounds stimulate PG synthesis and enhance the PGH2/PGG2 ratio. As oxygen radicals are liberated during the conversion of PGG2 to PGH2 it is suggested that the less acidic methane sulfonanilides are scavengers of the (pro-inflammatory) oxygen radicals.

Animals↗

PubMed1983

Effects of several anti-inflammatory drugs on the various parameters involved in the inflammatory response in rat carrageenin-induced pleurisy.

In rat carrageenin pleurisy, both steroidal and non-steroidal anti-inflammatory drugs (SAID and NSAID respectively) produced a dose-related reduction of exudate volume and of prostaglandin (PG)E2 contents in the exudate at 3 h after carrageenin. However, with the exception of ketoprofen, administration of all the NSAID in low doses resulted in a significant reduction of PGE2 contents with no significant reduction in exudate volume. NSAID reduced leucocyte number and total activities of lysosomal enzymes in the exudate at 3 h after carrageenin only at the higher doses, while SAID did so in a dose-related manner. Both SAID and NSAID reduced the arylsulfatase activity released into the exudate (free activity) dose-relatedly but not the free activity of beta-glucuronidase at 3 h after carrageenin. However, some drug treatments resulted in a lower reduction in free arylsulfatase activity than in exudate volume. These results suggest that the reduction of PGE2 contents may be the main contribution to the anti-exudative activities of anti-inflammatory drugs in rat carrageenin pleurisy and that this effect may be complemented by the reduction of free activity of lysosomal enzymes such as arylsulfatase.

Animals↗

PubMedDate not supplied

Effects of anti-inflammatory drugs and agents that modify intracellular transduction signals or metabolic activities in inflammatory cells on interleukin-1 induced cartilage proteoglycan resorption in vitro.

The actions of (a) anti-inflammatory drugs possessing a wide range of chemical structures and pharmacological actions, and (b) agents which modify intracellular transduction signals or metabolic functions were investigated for their potential to modify in vitro the proteoglycan (PrGn) resorption in bovine nasal cartilage induced by interleukin-1 alpha (IL-1). It was found that: (a) none of the conventional anti-inflammatory agents exhibited any inhibitory effects on IL-1 induced resorption of PrGns with the exception of the weak effects observed with the iron chelator, desferrioxamine, a cryogenine derivative JB-1-0, and myalex; (b) the antitumour agent cisplatin was a potent inhibitor but the analogue, transplatin, which does not inhibit DNA synthesis was without effect; (c) suramin, an inhibitor of cartilage degrading enzymes from leucocytes, also inhibited IL-1 induced resorption, as did natural somatomedin C (insulin-like growth factor = IGF alpha) but not agents previously shown to inhibit the lymphocyte mitogenic responses to IL-1 (e.g. alpha-melanocyte stimulating hormone, phenylglyoxal); (d) while no effects were observed with drugs that alter the intracellular production of cyclic AMP, those which affect uptake of calcium ions did inhibit proteoglycan resorption by IL-1. The results suggest that IL-1 induced cartilage PrGn degradation can be regulated at the level of transcriptional production of intracellular PrGn degrading enzymes or their activity, regulating calcium uptake into chondrocytes or by overcoming the PrGn degradation from IL-1 by stimulating the synthesis of these macromolecules.

Animals↗

PubMed1993

An in vitro method for assessing the effects of pro-inflammatory and anti-inflammatory compounds on microvascular permeability in the rat small intestine.

A method is described in which the blood vessels of the rat mesentery and small intestine were perfused for 15 min in vitro with a gelatin-containing physiological salt solution. Colloidal carbon (CC) was then added to the perfusate. In control preparations, very little CC was trapped in the microvessels of the small intestine, but if platelet-activating factor (PAF) was added for 5 min before the infusion of CC, many microvessels were "blackened." When the PAF antagonist BN52021 was included in the perfusate throughout, the "blackening" response to PAF was significantly reduced. Using micrographs of fixed specimens of gut, the amounts of "blackening" in the microvessels of the villi, the crypts of Lieberkuhn, and the muscularis were assessed using semiautomated image analysis. The technique provides a means of investigating the effects on microvascular permeability of pro-inflammatory and anti-inflammatory compounds. It is particularly useful for testing substances which, because of their highly toxic nature, cannot be administered systemically in vivo.

Animals↗

PubMed2005

The effect of non-steroidal anti-inflammatory drugs on inflammatory cystoid macular edema.

PURPOSE: To assess the role of systemic non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of inflammatory cystoid macular edema (iCME). DESIGN: Pilot study. METHODS: We included 66 patients with iCME and treated them with naproxen (2 x 250 mg daily; n = 28) or rofecoxib (1 x 25 mg daily; n = 38). After 4 months of therapy, visual acuity and inflammation activity were measured. We evaluated the grade of CME, retinal vasculitis, and papillary leakage with fluorescein angiography. RESULTS: No clear effect of NSAIDs on iCME, visual acuity, and intraocular inflammation was observed. A beneficial effect was noted in less than 8% of the affected eyes. The drop-out rate after 4 months of treatment was 52%, because of adverse effects or inefficacy of the treatment. Improvement of visual acuity was slightly better in patients who were treated with naproxen compared with rofecoxib (P < or = .05). CONCLUSION: Systemic NSAIDs have a limited role (if any) in the treatment of iCME.

Adolescent↗

PubMed2005

Inflammatory properties of municipal effluents to Elliptio complanata mussels--lack of effects from anti-inflammatory drugs.

The purpose of this study was to identify the pharmacological effects of anti-inflammatory drugs in freshwater mussels (Elliptio complanata) exposed to a primary-treated municipal effluent. Mussel specimens were injected with either increasing concentrations of ibuprofen or with a municipal effluent extract, and then left to stand for 24 h at 15 degrees C. They were also exposed to dilutions of a primary-treated effluent for 30 days at 15 degrees C under semi-static conditions. Gill and gonad cylcooxygenase (COX) were then determined after the incubation period. The influence of various drugs found in municipal effluents on serotonin and dopamine synaptosome transport was determined in visceral ganglia. The results show that injections of ibuprofen reduced COX activity nearly 4-fold in gills and 1.4-fold in gonads. However, COX activity was induced in both tissues after 24 h in mussels injected with a municipal effluent extract and after 30 days in those exposed to dilutions of the effluent. Moreover, synaptosomal dopamine transport activity was increased by ibuprofen, aspirin, caffeine and estradiol-17beta (E2), and decreased by loperamide and carbamazepine, suggesting increased and decreased turnover rates of this catecholamine, respectively. Serotonin transport activity was much less affected, decreasing with high doses of loperamide and increasing with ibuprofen, but with less intensity than with dopamine. The results suggest that although ibuprofen can effectively reduce COX activity in gill and gonadal tissues, exposure to both the municipal effluent and its organic extract increased COX activities, indicating the absence of NSAID (non-steroidal anti-inflammatory drugs)-related effects. Besides their known estrogenic and serotonergic properties, municipal effluents appear to elicit a state similar to inflammation in freshwater mussels.

Animals↗

PubMed2006

Anti-inflammatory effect of all-trans-retinoic acid in inflammatory arthritis.

OBJECTIVE: To determine whether all-trans-retinoic acid (ATRA) improves the destruction of joints and the effect of cytokines on DBA/1J mice with collagen-induced arthritis (CIA). METHODS: Starting from the time of type II collagen injection, DBA/1J mice were injected intraperitoneally with PBS or 0.5 mg of ATRA 3 times per week for 35 days. The effects of treatment were monitored by determining arthritis and histological scores and measuring cellular proliferation, production of cytokines (IL-2, IL-10, IL-12, IL-6, IFN-gamma, and TNF-alpha) and IgG, and the expression of mRNAs for inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), and CXCR3. RESULTS: The arthritis score and incidence of arthritis were lower in the mice treated with ATRA than in those treated with PBS. Histopathologic evidence of joint damage was 34% lower, and the infiltrations of macrophages were reduced in the mice treated with ATRA compared with those treated with PBS. Type II collagen- and ConA-stimulated proliferation of spleen cells, the production of cytokines (IL-6, IL-12, and TNF-alpha), the serum levels of total IgG and IgG1 anti-collagen antibodies, and the expression of mRNAs for MCP-1 were significantly reduced in the mice treated with ATRA than in those treated with PBS. CONCLUSION: ATRA improved the clinical course and reduced the production of inflammatory cytokines, immunoglobulin, and chemokines in murine CIA. These data suggest that ATRA might be also effective for the treatment of inflammatory arthritis like human rheumatoid arthritis.

Animals↗

PubMed2006

Chemokine expression in human erythroid leukemia cell line AS-E2: macrophage inflammatory protein-3alpha/CCL20 is induced by inflammatory cytokines.

OBJECTIVE: Normal and malignant hematopoietic cells are shown to express and secrete various cytokines and chemokines, some of which are believed to play an important role in normal and abnormal hematopoiesis in an autocrine/paracrine manner. To explore the possibility of a cytokine/chemokine network participating in the pathophysiology of anemic disorders, we evaluated the ability of inflammatory cytokines to induce chemokine expression using erythroid progenitor cells. METHODS: Erythropoietin-dependent human leukemia cell line AS-E2 was used as a model of erythroid colony-forming unit (CFU-E) cells. The expression of mRNA of 8 chemokines was examined using RT-PCR, before and after TNF-alpha, IFN-gamma, and IL-1beta stimulation. For MIP-3alpha, the promoter activity was analyzed by luciferase assay and secretion was confirmed by ELISA. The expression of CCR6, the specific receptor for MIP-3alpha, was analyzed by RT-PCR and flow cytometry. RESULTS: Unstimulated AS-E2 cells constitutively expressed transcripts for MCP-4, IP-10, PF-4, IL-8, and MIP-3alpha. Stimulation with TNF-alpha, IFN-gamma, and IL-1beta upregulated MIP-3alpha mRNA expression and induced its protein secretion. Luciferase assay revealed that these cytokines could upregulate promoter activity of the MIP-3alpha gene, possibly through the NF-kappaB pathway. CCR6 mRNA was detected and its intracellular expression was confirmed. CONCLUSION: These data suggest that inflammatory cytokine-stimulated erythroid progenitors secrete MIP-3alpha, which may function in an autocrine/paracrine manner. Furthermore, the existence of intracellular CCR6 suggests the involvement in cytokine signaling of a MIP-3alpha-dependent internal autocrine mechanism. These mechanisms may play a role in pathophysiology of anemic disorders, such as secondary anemia and bone marrow failure syndromes.

Cell Line, Tumor↗

PubMed2004

Anti-inflammatory effects of alpha-melanocyte-stimulating hormone against rat endotoxin-induced uveitis and the time course of inflammatory agents in aqueous humor.

PURPOSE: We examined the effects of the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) on rat endotoxin-induced uveitis, and to measure the expression of inflammatory cytokines and chemokines with and without the alpha-MSH treatment over the course of the disease. METHODS: We injected Lewis rats once with Salmonella typhimurium lipopolysaccharide (LPS) to induce uveitis. The rats were given intravenous injections of 250, 500 or 1000 microg of alpha-MSH. The eyes were examined over the next 24 h for inflammation. Aqueous humor was collected 6, 12 and 24 h after endotoxin injections and the number of infiltrating cells were counted in anterior chamber. In addition, we assayed the concentration of protein, nitric oxide, TNF-alpha, IL-6, MCP-1 and MIP-2. RESULTS: Rats injected with alpha-MSH showed a significant decrease in the number of infiltrating cells in anterior chamber. Moreover, alpha-MSH-treated rats with endotoxin-induced uveitis (EIU) showed significantly lower concentrations of protein, nitric oxide, proinflammatory cytokines and chemokines in their aqueous humor. Even the early stages of EIU were suppressed by the injection of alpha-MSH. CONCLUSIONS: Our results demonstrate that the immunosuppressive neuropeptide alpha-MSH inhibits the early induction events of endotoxin-induced inflammation in the eye; therefore, suppresses the subsequent infiltration of cells and intraocular production of inflammatory cytokines and chemokines in eyes. alpha-MSH has a possibility of being a therapeutic strategy for anterior uveitis.

Animals↗