The Lectin Isolated from the Alga Hypnea cervicornis Promotes Antinociception in Rats Subjected to Zymosan-Induced Arthritis: Involvement of cGMP Signalization and Cytokine Expression.

This study investigated the effects of the alga lectin Hypnea cervicornis agglutinin (HCA) on rat zymosan-induced arthritis (ZyA). Zymosan (50-500 µg/25 µL) or sterile saline (Sham) was injected into the tibio-tarsal joint of female Wistar rats (180-200 g). Arthritic animals received morphine (4 mg/kg, intraperitoneal), indomethacin (5 mg/kg, intraperitoneal), or 2% lidocaine (100 µL, subcutaneous). HCA (0.3-3 mg/kg) was administered by intravenous route 30 min before or 2 h after zymosan. 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (ODQ, 4 µg, intra-articular) was given 30 min prior HCA. Hypernociception was measured every hour until 6 h, time in which animals were sacrificed for evaluation of leukocytes of the intra articular fluid and gene expression of TNF-α, IL-1, IL-10, and iNOS in the joint tissues using PCR techniques. Hypernociception was responsive to morphine and indomethacin, and its threshold was not altered by lidocaine. The post-treatment of HCA reduced both hypernociception and leukocyte influx. This antinociceptive effect was abolished either by ODQ and glibenclamide. HCA also reduced gene expression of iNOS and TNF-α. In conclusion, the antinociceptive effect of HCA in ZyA involves cyclic GMP signalization and selective modulation of cytokine expression.

Antioxidant, hepatoprotective, genoprotective, and cytoprotective effects of quercetin in a murine model of arthritis.

Rheumatoid arthritis is a highly debilitating inflammatory autoimmune disease which is characterized by joint destruction. The present study sought to investigate the effect of quercetin in rats with complete Freund's adjuvant-induced arthritis. Animals were divided into control/saline, control/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg) arthritis/saline, and arthritis/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg); the treatments were administered for 45 days. Biochemical, oxidative stress, genotoxicity, and cytotoxicity parameters were evaluated. All doses of quercetin reduced the levels of aspartate aminotransferase, thiobarbituric acid-reactive substances, and reactive oxygen species; however, only treatment with 25 or 50 mg/kg increased catalase activity. Total thiol and reduced glutathione levels were not significantly affected by the induction nor by the treatments. Genotoxicity assessed by DNA damage, and cytotoxicity through picogreen assay, decreased after treatments with quercetin. Our results present evidence of the antioxidant, cytoprotective, genoprotective and hepatoprotective, and effects of quercetin, demonstrating its potential as a candidate for coadjuvant therapy.

Terpenes as possible drugs for the mitigation of arthritic symptoms - A systematic review.

BACKGROUND: Arthritis is a syndrome associated with exacerbated inflammation, joint destruction and chronic pain and disability. Chronic treatment of arthritis is associated with several side effects and high abandonment. Therefore, there has been an ongoing search for alternative treatments to overcome these problems. PURPOSE: Natural products, which are already widely used for their biological, cosmetic and pharmacotechnic properties, are a possible source for new drugs. Terpenes, a large class of organic compounds produced mainly by plants and trees, are a promising natural product and have already been shown to be effective in treating chronic pain, particularly of an inflammatory origin. STUDY DESIGN AND METHODS: This review identifies the main terpenes with anti-arthritic activity reported in the last 10 years. A survey was conducted between December 2017 and June 2018 in the PUBMED, SCOPUS and Science Direct databases using combinations of the descriptors terpenes, arthritis and inflammation. RESULTS: The results showed that terpenes have promising biological effects in relation to the treatment of arthritis, with the 24 terpenes identified in our survey being effective in the modulation of inflammatory mediators important to the physiopathology of arthritis, such as IL-6, IL-17, TNF-α, NFκB, and COX-2, among others. It is important to note that most of the studies used animal models, which limits, at least in part, the direct translation to humans of the experimental evidence produced by the studies. CONCLUSION: Together, our finds suggest that terpenes can modulate the immuno-regulatory and destructive tissue events that underlie the clinical presentation and the progression of arthritis and are worthy of further clinical investigation.

Modulation of immune response to induced-arthritis by low-level laser therapy.

As low-level laser therapy immune cells responses are not always clarified, this study aimed to evaluate cytokines and immune cells profile after low-level laser therapy (LLLT) on arthritis-induced model. Arthritis was induced in C57BL/6 mice divided into five groups: euthanized 5 hours after inflammation induction; untreated; dexamethasone treated; LLLT at 3 Jcm-2 ; LLLT at 30 Jcm-2 . Cytokine measurements by enzyme-linked immunosorbent assay and mRNA cytokine relative levels by real-time quantitative polymerase chain reaction were performed with arthritic ankle (IL-1ß, IL-6, TNF-α, IL-10 and TGF-ß). Macrophages, dendritic cells, natural killer cells, lymphocytes CD4+ , CD8+ , Treg and costimulatory proteins were quantified in proximal lymph node by flow cytometry. Data showed decrease in all cytokine levels after LLLT and alteration in mRNA relative levels, depending on the energy density used. LLLT was able to increase of immune cell populations analyzed in the lymph node as well as costimulatory proteins expression on macrophages and dendritic cells. Treg TCD4+ and TCD8+ population enrichment were observed in LLLT at 3 and 30 Jcm-2 groups, respectively. Furthermore, Treg TCD8+ cells expressing higher levels of CD25 were observed at LLLT at 30 Jcm-2 group. Our results indicate that LLLT could change the inflammatory course of arthritis, tending to accelerate its resolution through immune cells photobiostimulation.

The P2X7 Receptor, Cathepsin S and Fractalkine in the Trigeminal Subnucleus Caudalis Signal Persistent Hypernociception in Temporomandibular Rat Joints.

Temporomandibular joint (TMJ) is frequently involved with rheumatoid arthritis with a high prevalence that could result in a chronic pain state. Once the disease is established in the joint, the antigen-specific immune reaction initiates a neuro-immune cascade of events that causes sensitization of the central nervous system. This study establishes animal experimental models that evaluate the chronicity of albumin-induced arthritis hypernociception in the TMJ. Antigen-induced arthritis was generated in rats with methylated bovine serum albumin (mBSA) diluted in complete Freund's. Intra-articular injection of mBSA (10 µg/TMJ/week) during 3 weeks resulted in a persistent inflammatory hypernociception which was characterized by an inflammatory episode characterized by the increased of lymphocytes, macrophages and pro-inflammatory interleukins IL-12 and IL-18. The persistent model of inflammatory hypernociception induced by arthritis in the TMJ elicited protein levels of P2X7 receptors, cathepsin S and fractalkine in the trigeminal subnucleus caudalis. Overall, the results of the present work suggest that a persistent inflammatory hypernociception of albumin-induced arthritis in the TMJ leads to the activation of the central nervous system signaling by P2X7/cathepsin S/fractalkine pathway.

Anti-Inflammatory Activity of a Polymeric Proanthocyanidin from Serjania schiedeana.

The ethyl acetate extract (SsAcOEt) from Serjania schiedeana, select fractions (F-6, F-12, F-13, F-14), and one isolated compound, were evaluated in 12-O-tetradecanoylphorbol 13-acetate (TPA) ear edema and kaolin/carrageenan (KC)-induced monoarthritis assays. SsEtOAc induced edema inhibition of 90% (2.0 mg/ear), fractions showed activity within a range of 67-89%. Due to the fact F-14 showed the highest effect, it was separated, yielding a proanthocyanidin-type called epicatechin-(4ß â†’ 8)-epicatechin-(4ß â†’ 8, 2ß â†’ O → 7) epicatechin (ETP). This compound (2.0 mg/ear) provoked 72% of edema inhibition (ED50 = 0.25 mg/ear, Emax = 52.9%). After 9 days of treatment, joint inflammation was decreasing, and on the last day, SsEtOAc (400 mg/kg), F-14 and ETP (10 mg/kg), SsEtOAc (200 mg/kg), methotrexate (MTX) 1.0 mg/kg and meloxicam (MEL) 1.5 mg/kg, produced an inhibition articulate edema of 94, 62, 36, 21, 80, and 54%, respectively. In the joint, pro-inflammatory molecules were elevated in animals without treatment (vehicle group, VEH). Treatments from S. schiedeana induced a decrease in the concentration of interleukin (IL)-1ß, IL-17, and IL-6, and SsEtOAc at a higher dose diminished tumor necrosis factor (TNF-α). IL-10 and IL-4 were fewer in the VEH group in comparison with healthy mice; the animals with treatments from S. schiedeana induced an increment in the levels of these cytokines in joint and spleen.

Two opposite extremes of adiposity similarly reduce inflammatory response of antigen-induced acute joint inflammation.

OBJECTIVE: Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known about the acute inflammatory response in joints that results from diet-induced adipose tissue remodeling. The objective of this study was to determine whether alterations in adipose tissue mass arising from food consumption modify the inflammatory response of antigen-induced joint inflammation in mice. METHODS: Male BALB/c mice were fed a chow diet, a highly refined carbohydrate-containing (HC) diet for 8 wk. They were then immunized and, after 2 wk, received a knee injection of methylated bovine serum albumin (mBSA). They were sacrificed at 6, 24, and 48 h after injection. The effect of the cafeteria diet for 8 wk, which also increases adipose tissue, or conjugated linoleic acid (CLA) supplementation for 4 wk, a model of lipodystrophy, was evaluated 24 h after knee challenge with mBSA. RESULTS: Cellular influx, predominantly neutrophils, in synovial fluid was attenuated in the HC diet group, as were levels of myeloperoxidase and IL-1ß in periarticular tissue and histopathological analysis. These responses were associated with reduced adiponectin and increased leptin in serum, which was pronounced in mice fed the HC diet. Cafeteria diet and CLA supplementation induced a profile similar to that seen with the HC diet in terms of inflammation, disease response, and metabolic alteration. Interestingly, after the injection of mBSA, the area of adipocytes in the infrapatellar fat pad increased in mice fed with chow diet similar to those fed the HC and cafeteria diet. CONCLUSIONS: We demonstrated that attenuation of joint response induced by diet was independent of adipose tissue remodeling but could be associated with metabolic alterations.

Baroreflex activation in conscious rats modulates the joint inflammatory response via sympathetic function.

The baroreflex is a critical physiological mechanism controlling cardiovascular function by modulating both the sympathetic and parasympathetic activities. Here, we report that electrical activation of the baroreflex attenuates joint inflammation in experimental arthritis induced by the administration of zymosan into the femorotibial cavity. Baroreflex activation combined with lumbar sympathectomy, adrenalectomy, celiac subdiaphragmatic vagotomy or splenectomy dissected the mechanisms involved in the inflammatory modulation, highlighting the role played by sympathetic inhibition in the attenuation of joint inflammation. From the immunological standpoint, baroreflex activation attenuates neutrophil migration and the synovial levels of inflammatory cytokines including TNF, IL-1ß and IL-6, but does not affect the levels of the anti-inflammatory cytokine IL-10. The anti-inflammatory effects of the baroreflex system are not mediated by IL-10, the vagus nerve, adrenal glands or the spleen, but by the inhibition of the sympathetic drive to the knee. These results reveal a novel physiological neuronal network controlling peripheral local inflammation.

Alpha-melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus-like model.

Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α-MSH analogue [Nle4, DPhe7]-α-MSH (NDP-MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and α-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of α-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP-MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option.

Protective effect of low-level laser therapy (LLLT) on acute zymosan-induced arthritis.

The aim of this study was to evaluate the effect of low-level laser therapy on acute zymosan-induced arthritis, with respect to the laser action on inflammatory cells influx, release of pro-inflammatory mediators, metalloproteinases activity into the joint cavity and the cartilage repair process. Arthritis was induced in male Wistar rats (250-280 g) by intra-articular injection of zymosan (1 mg dissolved in 50 µl of a sterile saline solution) into one rear knee joint. Animals were irradiated immediately, 1 and 2 h after zymosan administration with a semiconductor laser InGaAIP (660 nm, 10 mW, 2.5 J/cm(2), 10 s). In the positive control group, animals were injected with the anti-inflammatory drug dexamethasone 1 h prior to the zymosan administration. Treatment with laser significantly inhibited leukocytes influx, the release of IL-1 and IL-6 and also the activity of metalloproteinase-2 and 9, into the joint cavity. In conclusion, laser therapy was effective in reducing inflammation to sites of injury and inhibit activation of proteases (gelatinase) suggesting less degradation of collagen tissue in experimental model of acute arthritis.

Effect of tibiotarsal joint inflammation on gene expression and cross-sectional area in rat soleus muscle.

BACKGROUND: Joint inflammation is a common clinical problem in patients treated by physical therapists. The hypothesis of this study is that joint inflammation induces molecular and structural changes in the soleus muscle, which is composed mainly of slow-twitch muscle fibers. OBJECTIVE: To study the effect of tibiotarsal joint inflammation on muscle fiber cross-sectional area (CSA), gene expression levels (atrogin-1, MuRF1, MyoD, myostatin, p38MAPK, NFκB, TNF-alpha), and TNF-alpha protein in the soleus muscle. METHOD: Wistar rats were randomly divided into 3 periods (2, 7 and 15 days) and assigned to 4 groups (control, sham, inflammation, and immobilization). RESULTS: In the inflammation group at 2 days, MuRF1 and p38MAPK expression had increased, and NFκB mRNA levels had decreased. At 7 days, myostatin expression had decreased. At 7 and 15 days, this group had muscle fiber CSA reduction. At 2 days, the immobilization group showed increased atrogin-1, MuRF1, NFκB, MyoD, and p38MAPK expressions and reduced muscle fiber CSA. At 7 and 15 days, myostatin mRNA levels had increased, and the CSA had decreased. The sham group showed increased p38MAPK and myostatin expressions at 2 and 7 days, respectively. No changes occurred in TNF-alpha gene or protein expression. CONCLUSION: Acute joint inflammation induces gene expression related to the proteolytic pathway without reduction in muscle fiber CSA. Chronic joint inflammation induced muscle atrophy without up-regulation of important genes belonging to the proteolytic pathway. Thus, muscle adaptation may differ according to the stage of joint inflammation, which suggests that the therapeutic modalities used by physical therapists at each stage should also be different.

Effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation.

We have recently demonstrated that gonadal steroid hormones decrease formalin-induced temporomandibular joint nociception in rats. Given that the attenuation of inflammation is a potential mechanism underlying this antinociceptive effect, we evaluated the effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation. Plasma extravasation, a major sign of acute inflammation, and neutrophil migration, an important event related to tissue injury, were evaluated. Formalin induced significantly lower temporomandibular joint plasma extravasation and neutrophil migration in proestrus females than in males and in diestrus females. Since estradiol serum level is high in proestrus females and low in diestrus females and in males, these findings suggest that the high physiological level of estradiol decreases temporomandibular joint inflammation. Estradiol but not progesterone administration in ovariectomized females significantly decreased formalin-induced plasma extravasation and neutrophil migration, an effect that was blocked by the estrogen receptor antagonist ICI 182780. Plasma extravasation and neutrophil migration were not affected by orchiectomy, but testosterone or estradiol administration in orchidectomized males significantly decreased them. The androgen receptor antagonist flutamide blocked the anti-inflammatory effect of testosterone while ICI 182780 blocked that of estradiol in males. Previous intravenous administration of a nonspecific selectin inhibitor significantly decreased formalin-induced temporomandibular joint nociception and neutrophil migration in males, revealing a potent and positive correlation between temporomandibular joint nociception and inflammation. Taken together, these findings demonstrate a pronounced anti-inflammatory effect of estradiol and testosterone in the temporomandibular joint region and suggest that this effect may mediate, at least in part, the antinociceptive effect of these hormones.

Inflammatory and oxidative stress markers in experimental crystalopathy: their modification by photostimulation.

Crystalopathies are inflammatory pathologies caused by cellular reactions to the deposition of crystals in the joints. The anti-inflammatory effect of the helium-neon (He-Ne) laser and that of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, meloxicam, celecoxib, and rofecoxib was studied in acute and chronic arthritis produced by hydroxyapatite and calcium pyrophosphate in rats. The presence of the markers fibrinogen, L-citrulline, nitric oxide, and nitrotyrosine was determined. Crystals were injected into the posterior limb joints of the rats. A dose of 8 J/cm(2) of energy from an He-Ne laser was applied for 3 d in some groups and for 5 d in other groups. The levels of some of the biomarkers were determined by spectrophotometry, and that of nitrotyrosine was determined by ELISA. For statistical analysis, Fisher's exact test was used, and p +/- 0.05 was considered significant. In arthritic rats, the fibrinogen, L-citrulline, nitric oxide, and nitrotyrosine levels increased in comparison to controls and to the laser-treated arthritic groups (p +/- 0.001), (p +/- 0.001), (p +/- 0.02), and (p +/- 0.01), respectively. When comparing fibrinogen from arthritic rats with disease induced by hydroxyapatite with undiseased and arthritic rats treated with NSAIDs, the He-Ne laser decreased levels to values similar to those seen in controls (p +/- 0.01). Inflammatory and oxidative stress markers in experimental crystalopathy are positively modified by photobiostimulation.

Endothelins modulate inflammatory reaction in zymosan-induced arthritis: participation of LTB4, TNF-alpha, and CXCL-1.

Endothelins (ETs) are involved in inflammatory events, including pain, fever, edema, and cell migration. ET-1 levels are increased in plasma and synovial membrane of rheumatoid arthritis (RA) patients, but the evidence that ETs participate in RA physiopathology is limited. The present study investigated the involvement of ETs in neutrophil accumulation and edema formation in the murine model of zymosan-induced arthritis. Intra-articular (i.a.) administration of selective ET(A) or ET(B) receptor antagonists (BQ-123 and BQ-788, respectively; 15 pmol/cavity) prior to i.a. zymosan injection (500 microg/cavity) markedly reduced knee-joint edema formation and neutrophil influx to the synovial cavity 6 h and 24 h after stimulation. Histological analysis showed that ET(A) or ET(B) receptor blockade suppressed zymosan-induced neutrophil accumulation in articular tissue at 6 h. Likewise, dual blockade of ET(A)/ET(B) with bosentan (10 mg/kg, i.v.) also reduced edema formation and neutrophil counts 6 h after zymosan stimulation. Pretreatment with BQ-123 or BQ-788 (i.a.; 15 pmol/cavity) also decreased zymosan-induced TNF-alpha production within 6 h, keratinocyte-derived chemokine/CXCL1 production within 24 h, and leukotriene B(4) at both time-points. Consistent with the demonstration that ET receptor antagonists inhibit zymosan-induced inflammation, i.a. injection of ET-1 (1-30 pmol/cavity) or sarafotoxin S6c (0.1-30 pmol/cavity) also triggered edema formation and neutrophil accumulation within 6 h. Moreover, knee-joint synovial tissue expressed ET(A) and ET(B) receptors. These findings suggest that endogenous ETs contribute to knee-joint inflammation, acting through ET(A) and ET(B) receptors and modulating edema formation, neutrophil recruitment, and production of inflammatory mediators.

Chronic destructive elbow arthropathy associated with hydroxyapatite crystals in a patient with systemic lupus erythematosus.

We describe the case of a young woman with systemic lupus erythematosus (SLE) who presented with painful acute swelling and limited motion of the elbow. Analysis of synovial fluid exhibited a noninflammatory cell count, negative cultures, amorphous nonbirefringent particles, and a positive Alizarin red S staining. X-rays showed calcifications, spurring, sclerosis, and despite the short duration of symptoms, loss of radial-humeral and cubital-humeral joint spaces. The diagnosis of an acute attack within a chronic degenerative arthropathy of the elbow associated with hydroxyapatite crystals was established. Such crystal-induced arthropathy can be an occasional explanation for acute arthritis in SLE.

Evidence for the involvement of endogenous ATP and P2X receptors in TMJ pain.

Evidence is accumulating which supports a role for ATP in the initiation of pain by acting on P2X receptors expressed on nociceptive afferent nerve terminals. To investigate whether these receptors play a role in temporomandibular (TMJ) pain, we studied the presence of functional P2X receptors in rat TMJ by examining the nociceptive behavioral response to the application of the selective P2X receptor agonist alpha,beta-methylene ATP (alpha,beta-meATP) into the TMJ region of rat. The involvement of endogenous ATP in the development of TMJ inflammatory hyperalgesia was also determined by evaluating the effect of the general P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) on carrageenan-induced TMJ inflammatory hyperalgesia. Application of alpha,beta-meATP into the TMJ region of rats produced significant nociceptive responses that were significantly reduced by the co-application of lidocaine N-ethyl bromide quaternary salt, QX-314, (2%) or of the P2 receptor antagonist PPADS. Co-application of PPADS with carrageenan into the TMJ significantly reduced inflammatory hyperalgesia. The results indicate that functional P2X receptors are present in the TMJ and suggest that endogenous ATP may play a role in TMJ inflammatory pain mechanisms possibly by acting primarily in these receptors.

Perfusion pressure in kidneys of arthritic rats and the influence of L-NAME.

Kidneys of control and arthritic rats were perfused with a hemoglobin-free perfusion fluid with simultaneous monitoring of perfusion pressure and oxygen uptake. The basal values of renal perfusion pressure were 76.3 +/- 4.63 and 59.96 +/- 3.65 mm Hg in control and arthritic rats, respectively. Infusion of 100 microM Nomega-nitro-L-arginine methyl ester (L-NAME) an inhibitor of constitutive and inducible nitric oxide synthase, increased the renal perfusion pressure to 91.6 +/- 5.52 and 106.69 +/- 8.47 mm Hg in control and arthritic rats, respectively. Oxygen uptake of kidneys from control rats was 2.48 +/- 0.74 micromol min(-1) g(-1) and that of the arthritic rats was 2.44 +/- 0.75 micromol min(-1) g(-1). These results are consistent with an increased production of hemodynamically active nitric oxide in kidneys of arthritic rats.

PAF modulates eicosanoids and TNF release in immune-complex arthritis in rats.

The participation of lipid mediators and tumor necrosis factor (TNF) on an experimental model of immune-complex arthritis was investigated. Male Wistar rats received intraarticular injection of rabbit antibodies to bovine serum albumin into the knee joint followed by i.v. injection of the antigen. The levels of eicosanoids and TNF released into the synovial exudates were then assessed using ELISA and the L929 lytic cell assay, respectively. Increase in the levels of LTB4, TXB2 and PGE2 were detected 5 min, 5 min, and 6 h after arthritis induction, respectively. Pretreatment with the PAF receptor antagonist WEB 2170 decreased the levels of PGE2 and increased those of LTB4, without altering TXB2 levels. Increase in the levels of TNF was detected at 3 h of arthritis. Pretreatment with either the cycloxygenase inhibitor indomethacin or the 5-lipoxygenase inhibitor L-663,536 had no effect on TNF levels. Pretreatment with WEB 2170 significantly decreased TNF levels. These results are the first demonstration of eicosanoids and TNF release in immune-complex arthritis. The data also suggest that PAF had both a positive and negative modulatory role on the release of PGE2 and LTB4, respectively. Moreover, TNF release into the synovial exudate did not depend on eicosanoids whereas platelet activating factor (PAF) appeared to mediate the release of this cytokine in the model.

Slow-reacting substance of anaphylaxis (SRS-A) activity in the synovial fluids of rabbits with antigen-induced arthritis.

Synovial fluids from rabbits with antigen-induced arthritis were investigated for the presence of slow-reacting substance of anaphylaxis (SRS-A) using biological assay in guinea-pig ileum. Inflamed joints from rabbits sacrificed within eight hours of the articular challenge disclosed SRS-A activity, indicating that peptidic leukotrienes may also be important in the physiopathology of acute articular inflammatory processes.