L'arthrose érosive des doigts [Erosive hand osteoarthritis].

Erosive hand osteoarthritis is common and debilitating. Diagnosis is based on the presence of bone erosions which can appear late. Ultrasonography allows earlier diagnosis. The presence of apatite deposits could be of poor prognosis. Non pharmacological treatment includes the explanation of the inflammatory phenomena involved and the use of splints and physical therapy. Drug therapy includes analgesics, NSAIDs and infiltration of a steroid. Chondroitin sulfates have an analgesic and functional effect proven. DMARDs such as hydroxychloroquine and methotrexate have been used successfully. Some patients also benefited from isotope synoviortheses. New therapeutic ways, based on the pathophysiology of the disease, are new under evaluation.

Association of statins with inflammatory cytokines: a population-based Colaus study.

PURPOSE: A pleiotropic effect of statins has been reported in numerous studies. However, the association between statin use and inflammatory cytokines is controversial. We examined the associations between statin use and C-reactive protein (CRP), tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in a healthy Caucasian population. METHODS: Cross-sectional study of 6184 participants aged 35-75years from Lausanne, Switzerland. Cytokines were assessed by multiplexed particle-based flow cytometric assay. Self-reported history of medication was collected for statins and other medication. 99 participants without cytokine data were excluded. RESULTS: Among the 6085 participants, 2289 (37.6%), 451 (7.4%) and 43 (0.7%) had IL-1β, IL-6 and TNF-α levels below detection limits, respectively. On multivariate analysis adjusting for age, gender, smoking status, body mass index, hypertension, diabetes, baseline cardiovascular disease, total cholesterol, anti-inflammatory use, other cytokine modifying drugs and other drugs, participants on statins had significantly lower CRP levels (adjusted mean±standard error: 1.22±1.05 vs. 1.38±1.04mg/L for use and non-use, respectively, p<0.01 on log-transformed data). Conversely, no association was found between statin use and IL-1β (p=0.91), IL-6 (p=0.25) or TNF-α (p=0.28) levels. On multivariate analysis, individuals in the statin group (β coefficient=-0.12; 95% CI=-0.21, -0.03) had lower levels of CRP as compared to those in the reference group (i.e. those not using statin). However, no significant associations were observed between IL-1β, IL-6 and TNF-α and statins. CONCLUSION: Individuals on statins have lower CRP levels; conversely, no effect was found for IL-1β, IL-6 and TNF-α levels.

Understanding the multifaceted role of inflammatory mediators in ischemic stroke.

The evolution of ischemic brain damage is strongly affected by an inflammatory reaction that involves soluble mediators, such as cytokines and chemokines, and specialized cells activated locally or recruited from the periphery. The immune system affects all phases of the ischemic cascade, from the acute intravascular reaction due to blood flow disruption, to the development of brain tissue damage, repair and regeneration. Increased endothelial expression of adhesion molecules and blood-brain barrier breakdown promotes extravasation and brain recruitment of blood-borne cells, including macrophages, neutrophils, dendritic cells and T lymphocytes, as demonstrated both in animal models and in human stroke. Nevertheless, most anti-inflammatory approaches showing promising results in experimental stroke models failed in the clinical setting. The lack of translation may reside in the redundancy of most inflammatory mediators, exerting both detrimental and beneficial functions. Thus, this review is aimed at providing a better understanding of the dualistic role played by each component of the inflammatory/immune response in relation to the spatio-temporal evolution of ischemic stroke injury.

Delta-9-tetrahydrocannabinol (THC) protects partly against demyelination by modulating the inflammatory response: an in vitro study in aggregating brain cell cultures

Delta 9-tetrahydrocannabinol (THC) has been proposed as therapeutic agent in the treatment of multiple sclerosis. In the present study, we examined whether a modulation of brain inflammatory by THC may protect against demyelination. Myelinating aggregating brain cell cultures were subjected to demyelination by a repeated treatment (3x) with the two inflammatory agents interferon-y (IFN-y) and lipopolysaccharide (LPS). The effects of THC on an acute inflammatory reponse were also examined by treating the aggregates with a single application of the two inflammatory agents. THC effects on the demyelinating process and on several mediators of the inflammatory reponse were analyzed. THC treatment partially prevented the decreased immunoreactivity for MBP, and the decrease in MBP content measured by immunoblotting. It prevented IFN-y + LPS -induced microglial reactivity; and decreased the IFN-y + LPS-induced i8ncreased phosphorylation of p44/42 MAP kinase. The other inflammatory markers, I-NOS and TNF-a mRNA expression, and p38 MAP kinase phosphorylation of p44/42 MAP kinase. The other inflammatory markers, I-NOS and TNF-a mRNA expression, and p38 MAP kinase phosphorylation were downregulated by THC treatment following a single application of the inflammatory agents, but not after repeated applications. THC protected partially against the IFN-y + LPS-induced demyelination. The protective effect of THC on IFN-y + LPS-induced demyelination may be due to a decrease of the inflammatory reponse. However, the anti-inflammatory effect of THC on some inflammatory markers is lost when the inflammatory response is more proeminent and of longer duration, suggesting either that the anti-inflammatory effect of a molecule may depend on the properties of the inflammatory response, or that the anti-inflammatory potential of THC decreases in case of repeated exposure.

Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal.

Proteasome inhibition reduces proliferation, collagen expression, and inflammatory cytokine production in nasal mucosa and polyp fibroblasts

Proteasome inhibitors, used in cancer treatment for their proapoptotic effects, have anti-inflammatory and antifibrotic effects on animal models of various inflammatory and fibrotic diseases. Their effects in cells from patients affected by either inflammatory or fibrotic diseases have been poorly investigated. Nasal polyposis is a chronic inflammatory disease of the sinus mucosa characterized by tissue inflammation and remodeling. We tested the hypothesis that proteasome inhibition of nasal polyp fibroblasts might reduce their proliferation and inflammatory and fibrotic response. Accordingly, we investigated the effect of the proteasome inhibitor Z-Leu-Leu-Leu-B(OH)2 (MG262) on cell viability and proliferation and on the production of collagen and inflammatory cytokines in nasal polyp and nasal mucosa fibroblasts obtained from surgery specimens. MG262 reduced the viability of nasal mucosa and polyp fibroblasts concentration- and time-dependently, with marked effects after 48 h of treatment. The proteasome inhibitor bortezomib provoked a similar effect. MG262-induced cell death involved loss of mitochondrial membrane potential, caspase-3 and poly(ADP-ribose) polymerase activation, induction of c-Jun phosphorylation, and mitogen-activated protein kinase phosphatase-1 expression. Low concentrations of MG262 provoked growth arrest, inhibited DNA replication and retinoblastoma phosphorylation, and increased expression of the cell cycle inhibitors p21 and p27. MG262 concentration-dependently inhibited basal and transforming growth factor-β-induced collagen mRNA expression and interleukin (IL)-1β-induced production of IL-6, IL-8, monocyte chemoattractant protein-1, regulated on activation normal T cell expressed and secreted, and granulocyte/macrophage colony-stimulating factor in both fibroblast types. MG262 inhibited IL-1β/tumor necrosis factor-α-induced activation of nuclear factor-κB. We conclude that noncytotoxic treatment with MG262 reduces the proliferative, fibrotic, and inflammatory response of nasal fibroblasts, whereas high MG262 concentrations induce apoptosis.

Proteasome inhibition reduces proliferation, collagen expression, and inflammatory cytokine production in nasal mucosa and polyp fibroblasts

Proteasome inhibitors, used in cancer treatment for their proapoptotic effects, have anti-inflammatory and antifibrotic effects on animal models of various inflammatory and fibrotic diseases. Their effects in cells from patients affected by either inflammatory or fibrotic diseases have been poorly investigated. Nasal polyposis is a chronic inflammatory disease of the sinus mucosa characterized by tissue inflammation and remodeling. We tested the hypothesis that proteasome inhibition of nasal polyp fibroblasts might reduce their proliferation and inflammatory and fibrotic response. Accordingly, we investigated the effect of the proteasome inhibitor Z-Leu-Leu-Leu-B(OH)2 (MG262) on cell viability and proliferation and on the production of collagen and inflammatory cytokines in nasal polyp and nasal mucosa fibroblasts obtained from surgery specimens. MG262 reduced the viability of nasal mucosa and polyp fibroblasts concentration- and time-dependently, with marked effects after 48 h of treatment. The proteasome inhibitor bortezomib provoked a similar effect. MG262-induced cell death involved loss of mitochondrial membrane potential, caspase-3 and poly(ADP-ribose) polymerase activation, induction of c-Jun phosphorylation, and mitogen-activated protein kinase phosphatase-1 expression. Low concentrations of MG262 provoked growth arrest, inhibited DNA replication and retinoblastoma phosphorylation, and increased expression of the cell cycle inhibitors p21 and p27. MG262 concentration-dependently inhibited basal and transforming growth factor-β-induced collagen mRNA expression and interleukin (IL)-1β-induced production of IL-6, IL-8, monocyte chemoattractant protein-1, regulated on activation normal T cell expressed and secreted, and granulocyte/macrophage colony-stimulating factor in both fibroblast types. MG262 inhibited IL-1β/tumor necrosis factor-α-induced activation of nuclear factor-κB. We conclude that noncytotoxic treatment with MG262 reduces the proliferative, fibrotic, and inflammatory response of nasal fibroblasts, whereas high MG262 concentrations induce apoptosis.

A química medicinal de N-acilidrazonas: novos compostos-protótipos de fármacos analgésicos, antiinflamatórios e anti-trombóticos

In this article are described new bioactive N-acylhydrazone (NAH) derivatives, structurally designed as optimization of aryl hydrazones precursors planned by molecular hybridization of two 5-lipoxigenase inhibitors, e.g. CBS-1108 and BW-755c. The analgesic, antiedematogenic and anti-platelet aggregating profile of several isosteric compounds was investigated by using classic pharmacological assays in vivo and ex-vivo, allowing to identify new potent peripheric analgesic lead, a new anti-inflammatory and an antithrombotic agent. During this study was discovered dozen of active NAH compounds clarifying the structure-activity relationship for this series of NAH derivatives, indicating the pharmacophore character of the N-acylhydrazone functionality.

Constituintes químicos das folhas e avaliação da atividade anti-inflamatória de extratos das raízes e folhas de Guettarda pohliana Müll. Arg. (Rubiaceae)

This phytochemical investigation of Guettarda pohliana leaves led to the isolation of the triterpenes pomolic acid, rotundic acid, 3β,6α,19α,23-tetrahydroxyurs-12-en-28-oic acid, clethric acid, ursolic acid and oleanolic acid, the monoterpenoids loliolide and secoxyloganin, besides daucosterol and steroids. The structures of the isolated compounds were assigned on the basis of NMR data, including two-dimensional NMR methods. The anti-inflammatory activity of the crude methanolic extracts from leaves and roots, as well as of their fractions, was evaluated.

Estudo fitoquímico e avaliação da atividade anti-inflamatória de Aeschynomene fluminensis vell. (Fabaceae)

Phytochemical investigation of Aeschynomene fluminensis leaves and branches led to isolation of the flavonoid glycosides kaempferol 3,7-di-O-α-L-rhamnopyranoside, kaempferol 7-O-α-L-rhamnopyranoside, kaempferol 3-O-apiofuranosil-7-O- rhamnopyranoside, quercitin 3-O-α-L-rhamnopyranoside, quercitin 3-O-arabinofuranoside, 8-β-D-glucopyranosyl 4',5,7-trihydroxyflavanone, the isoflavonoid 4',7-di-hydroxy-isoflavone, the dimer epicatechin-(2β→7, 4β→8)- epicatechin, the polyol 3-O-methyl-chiro-inositol and two steroids in sitosterol and stigmasterol mixture. These compounds were identified by NMR ¹H and 13C and compared with literature data. Anti-inflammatory activity of the crude methanolic extract and its fractions was evaluated.

Constituintes químicos e avaliação das atividades antioxidante e anti-inflamatória das raízes de Sabicea brasiliensis wernh (Rubiaceae)

The phytochemical investigation of Sabicea brasiliensis roots led to the isolation of 5-O-caffeoylquinic acid, 3,5- and 4,5-O-dicaffeoylquinics acids, scopoletin, ursolic acid, a mixture of β-sitosterol, stigmasterol and campesterol, daucosterol and saccharose. The structures of the isolated compounds were assigned on the basis of one- and two-dimensional NMR spectroscopic methods and by comparison with literature data. The anti-inflammatory and antioxidant activities of the crude methanolic extract and its fractions were analyzed.

Chronic intrathecal cannulation enhances nociceptive responses in rats

The influence of a chronically implanted spinal cannula on the nociceptive response induced by mechanical, chemical or thermal stimuli was evaluated. The hyperalgesia in response to mechanical stimulation induced by carrageenin or prostaglandin E2 (PGE2) was significantly increased in cannulated (Cn) rats, compared with naive (Nv) or sham-operated (Sh) rats. Only Cn animals presented an enhanced nociceptive response in the first phase of the formalin test when low doses were used (0.3 and 1%). The withdrawal latency to thermal stimulation of a paw inflamed by carrageenin was significantly reduced in Cn rats but not in Nv or Sh rats. In contrast to Nv and Sh rats, injection in Cn animals of a standard non-steroid anti-inflammatory drug, indomethacin, either intraperitoneally or into the spinal cord via an implanted cannula or by direct puncture of the intrathecal space significantly blocked the intensity of the hyperalgesia induced by PGE2. Cannulated animals treated with indomethacin also showed a significant inhibition of second phase formalin-induced paw flinches. Histopathological analysis of the spinal cord showed an increased frequency of mononuclear inflammatory cells in the Cn groups. Thus, the presence of a chronically implanted cannula seems to cause nociceptive spinal sensitization to mechanical, chemical and thermal stimulation, which can be blocked by indomethacin, thus suggesting that it may result from the spinal release of prostaglandins due to an ongoing mild inflammation.

Mechanisms in anti-inflammation and resolution: the role of lipoxins and aspirin-triggered lipoxins

Multicellular host responses to infection, injury or inflammatory stimuli lead to the formation of a broad range of chemical mediators by the host. The integrated response of the host is essential to health and disease; thus it is important to achieve a more complete understanding of the molecular and cellular events governing the formation and actions of endogenous mediators of resolution that appear to control the duration of inflammation. Lipoxins are trihydroxytetraene-containing lipid mediators that can be formed during cell-cell interactions and are predominantly counterregulators of some well-known mediators of inflammation. Since this circuit of lipoxin formation and action appears to be of physiological relevance for the resolution of inflammation, therapeutic modalities targeted at this system are likely to have fewer unwanted side effects than other candidates and current anti-inflammatory therapies. Here, we present an overview of the recent knowledge about the biosynthesis and bioactions of these anti-inflammatory lipid mediators.

Long-term ethanol intoxication reduces inflammatory responses in rats

The anti-inflammatory effects of long-term ethanol intoxication were determined during ethanol treatment and withdrawal on the basis of neutrophil and eosinophil migration, hind paw edema and mast cell degranulation. Male Wistar rats (180-200 g, around 2 months of age) were exposed to increasing concentrations of ethanol vapor over a 10-day period. One group was evaluated immediately after exposure (treated group - intoxicated), and another was studied 7 h later (withdrawal group). Ethanol inhalation treatment significantly inhibited carrageenan- (62% for the intoxicated group, N = 5, and 35% for the withdrawal group, N = 6) and dextran-induced paw edema (32% for intoxicated rats and 26% for withdrawal rats, N = 5 per group). Ethanol inhalation significantly reduced carrageenan-induced neutrophil migration (95% for intoxicated rats and 41% for withdrawn rats, N = 6 per group) into a subcutaneous 6-day-old air pouch, and Sephadex-induced eosinophil migration to the rat peritoneal cavity (100% for intoxicated rats and 64% for withdrawn rats, N = 6 per group). A significant decrease of mast cell degranulation was also demonstrated (control, 82%; intoxicated, 49%; withdrawn, 51%, N = 6, 6 and 8, respectively). Total leukocyte and neutrophil counts in venous blood increased significantly during the 10 days of ethanol inhalation (leukocytes, 13, 27 and 40%; neutrophils, 42, 238 and 252%, respectively, on days 5, 9 and 10, N = 7, 6 and 6). The cell counts decreased during withdrawal, but were still significantly elevated (leukocytes, 10%; neutrophils, 246%, N = 6). These findings indicate that both the cellular and vascular components of the inflammatory response are compromised by long-term ethanol intoxication and remain reduced during the withdrawal period.

Lung hyperinflation stimulates the release of inflammatory mediators in spontaneously breathing subjects

Lung hyperinflation up to vital capacity is used to re-expand collapsed lung areas and to improve gas exchange during general anesthesia. However, it may induce inflammation in normal lungs. The objective of this study was to evaluate the effects of a lung hyperinflation maneuver (LHM) on plasma cytokine release in 10 healthy subjects (age: 26.1 ± 1.2 years, BMI: 23.8 ± 3.6 kg/m²). LHM was performed applying continuous positive airway pressure (CPAP) with a face mask, increased by 3-cmH2O steps up to 20 cmH2O every 5 breaths. At CPAP 20 cmH2O, an inspiratory pressure of 20 cmH2O above CPAP was applied, reaching an airway pressure of 40 cmH2O for 10 breaths. CPAP was then decreased stepwise. Blood samples were collected before and 2 and 12 h after LHM. TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12 were measured by flow cytometry. Lung hyperinflation significantly increased (P < 0.05) all measured cytokines (TNF-α: 1.2 ± 3.8 vs 6.4 ± 8.6 pg/mL; IL-1β: 4.9 ± 15.6 vs 22.4 ± 28.4 pg/mL; IL-6: 1.4 ± 3.3 vs 6.5 ± 5.6 pg/mL; IL-8: 13.2 ± 8.8 vs 33.4 ± 26.4 pg/mL; IL-10: 3.3 ± 3.3 vs 7.7 ± 6.5 pg/mL, and IL-12: 3.1 ± 7.9 vs 9 ± 11.4 pg/mL), which returned to basal levels 12 h later. A significant correlation was found between changes in pro- (IL-6) and anti-inflammatory (IL-10) cytokines (r = 0.89, P = 0.004). LHM-induced lung stretching was associated with an early inflammatory response in healthy spontaneously breathing subjects.