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PubMed2002

Pro-inflammatory and anti-inflammatory cytokine increases after spinal instrumentation surgery.

We investigated the effects of instrumentation on postoperative inflammatory reaction and identified standard changes in serum cytokine concentrations after spinal surgery. Pro-inflammatory cytokines [interleukin (IL)-6 and IL-8] and anti-inflammatory cytokines [IL-10, IL-1 receptor antagonist (ra), and soluble tumor necrosis factor receptors (sTNF-R) I and II] were assayed in serum from seven patients with lumbar spinal posterior decompression, six with spinal decompression and posterolateral fusion without instrumentation and seven with spinal decompression and posterolateral fusion with instrumentation. All cytokines after spinal instrumentation increased significantly more than in other groups on postoperative days 0 and 1. Seven days after SI, IL-6, -8, and -10 had normalized, but IL-1ra and sTNF-RI and sTNF-RII remained elevated. Both pro-inflammatory and anti-inflammatory cytokines were enhanced by implants in the acute phase, whereas only anti-inflammatory cytokines were enhanced by instruments in the subacute phase.

Aged↗

PubMed2006

Polymorphonuclear leucocytes selectively produce anti-inflammatory interleukin-1 receptor antagonist and chemokines, but fail to produce pro-inflammatory mediators.

The role of neutrophils in the immune response has long been regarded as mainly phagocytic, but recent publications have indicated the production of several cytokines by polymorphonuclear leucocytes (PMN). The results of the individual reports, however, vary considerably. In this study, we established a cytokine profile of pure human neutrophils and demonstrated that minor contamination of peripheral blood mononuclear cells (PBMCs) in PMN preparations can lead to false-positive results. In our hands, peripheral blood PMN fail to produce the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha). Instead, they secrete large amounts of the chemokine IL-8 and the anti-inflammatory IL-1 receptor antagonist (IL-1ra). Additionally, PMN preparations of a high purity show production of the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and growth-related oncogene-alpha (GRO-alpha), as well as macrophage colony-stimulating factor (M-CSF). The neutrophil therefore represents a novelty by producing the antagonist of IL-1beta (i.e. IL-1ra) in the absence of IL-1beta itself. To support our results, we differentiated stem cells from human cord blood into PMN and monocytes, respectively. These in vitro-differentiated PMN showed the same cytokine profile as peripheral blood PMN lacking IL-1beta, while differentiated monocytes produced the expected IL-1beta in addition to IL-1ra. The clear anti-inflammatory nature of their cytokine profile enables PMN to antagonize pro-inflammatory signals in experimental conditions. It is therefore possible that PMN play a key role in immune regulation by counteracting a dysregulation of the inflammatory process. Clinical studies, in which administration of recombinant G-CSF had a favourable effect on the outcome of severe infections and even sepsis without worsening inflammation, could thus be explained by our results.

Antigens, CD34↗

PubMed2005

Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva.

OBJECTIVES: The primary aetiologic factor of periodontal disease is the bacterial biofilm. Gram-positive and gram-negative bacteria possess a plethora of structural or secreted components that may cause direct destruction to periodontal tissues or stimulate host cells to activate a wide range of inflammatory responses. These responses are intended to eliminate the microbial challenge, but may often cause further tissue damage. METHODS: This review has been divided into three parts: (a) bacterial virulence factors, which includes basic information on bacterial virulence factors, and the principle inflammatory responses that host cells elicit against these factors, (b) main receptors and signalling pathways, which includes basic information about the main receptors that interact with the bacterial virulence factors, the nature of these interactions, and the activated signalling pathways that lead to inflammatory responses, and (c) initiation of inflammation, which includes a model by which the virulence factors may interact with host cells and lead to inflammatory responses in the gingiva. FINDINGS AND CONCLUSIONS: Bacterial components/virulence factors may be involved in modulating inflammatory responses and include: lipopolysaccharides (LPS), peptidoglycans, lipotechoic acids, fimbriae, proteases, heat-shock proteins, formyl-methionyl peptides, and toxins. Potential host cell receptors involved in recognizing bacterial components and initiating signalling pathways that lead to inflammatory responses include: Toll-like receptors (TLRs), CD14, nucleotide-binding oligomerization domain proteins (Nod) and G-protein-coupled receptors, including formyl-methionyl peptide receptors and protease-activated receptors. Of the above bacterial and host molecules, evidence from experimental animal studies implicate LPS, fimbriae, proteases, TLRs, and CD14 in periodontal tissue or alveolar bone destruction. However, evidence verifying the involvement of any of the above molecules in periodontal tissue destruction in humans does not exist.

Bacteria, Anaerobic↗

PubMed2007

Green tea increases anti-inflammatory tristetraprolin and decreases pro-inflammatory tumor necrosis factor mRNA levels in rats.

BACKGROUND: Tristetraprolin (TTP/ZFP36) family proteins have anti-inflammatory activity by binding to and destabilizing pro-inflammatory mRNAs such as Tnf mRNA, and represent a potential therapeutic target for inflammation-related diseases. Tea has anti-inflammatory properties but the molecular mechanisms have not been completely elucidated. We hypothesized that TTP and/or its homologues might contribute to the beneficial effects of tea as an anti-inflammatory product. METHODS: Quantitative real-time PCR was used to investigate the effects of green tea (0, 1, and 2 g solid extract/kg diet) on the expression of Ttp family genes (Ttp/Tis11/Zfp36, Zfp36l1/Tis11b, Zfp36l2/Tis11d, Zfp36l3), pro-inflammatory genes (Tnf, Csf2/Gm-csf, Ptgs2/Cox2), and Elavl1/Hua/Hur and Vegf genes in liver and muscle of rats fed a high-fructose diet known to induce insulin resistance, oxidative stress, inflammation, and TNF-alpha levels. RESULTS: Ttp and Zfp36l1 mRNAs were the major forms in both liver and skeletal muscle. Ttp, Zfp36l1, and Zfp36l2 mRNA levels were more abundant in the liver than those in the muscle. Csf2/Gm-csf and Zfp36l3 mRNAs were undetectable in both tissues. Tea (1 g solid extract/kg diet) increased Ttp mRNA levels by 50-140% but Tnf mRNA levels decreased by 30% in both tissues, and Ptgs2/Cox2 mRNA levels decreased by 40% in the muscle. Tea (2 g solid extract/kg diet) increased Elavl1/Hua/Hur mRNA levels by 40% in the liver but did not affect any of the other mRNA levels in liver or muscle. CONCLUSION: These results show that tea can modulate Ttp mRNA levels in animals and suggest that a post-transcriptional mechanism through TTP could partially account for tea's anti-inflammatory properties. The results also suggest that drinking adequate amounts of green tea may play a role in the prevention of inflammation-related diseases.

Journal Article↗

PubMed2004

[Quality of life in patients with inflammatory bowel diseases: translation to Portuguese language and validation of the "Inflammatory Bowel Disease Questionnaire" (IBDQ)].

BACKGROUND: Crohn's disease comprises, together with ulcerative colitis, the inflammatory bowel diseases, which because their morbidity and chronic evolution have a considerable impact on the patient's quality of life. The measurement of quality of life requires the determination of the degree of subjective well-being attributed to the lack of symptoms, to psychological state and daily activity, and is useful as an instrument of evaluation, both in clinical trials and health programs. Inflammatory Bowel Disease Questionnaire is an instrument developed by North-American investigators of McMaster University which reproducibility and validity has been determined in several countries studies, and has shown its use in the measurement of the quality of life of patients with inflammatory bowel diseases. AIMS: Our purpose was to translate that instrument into Portuguese language, its adaptation to Brazilian culture and verify its psychometric properties (validity and reproducibility). METHODS: It was applied to a population of 50 inflammatory bowel diseases patients (24 with Crohn's disease, 26 with ulcerative colitis). To test the criteria and construction validity of the instrument's, it was compared with SF-36, a general questionnaire for establishing quality of life, and the Crohn's Disease Activity Index and Lichtiger's Index. RESULTS: The correlations obtained were mostly moderate. About the intestinal diseases activity index, Lichtiger's index showed better correlations than Crohn's Disease Activity Index. To evaluate its reproducibility, the instrument was applied on three occasions, twice by the same observer (12 days average between applications) and once by a second observer, resulting in a high degree of intra- and interobserver correlation. CONCLUSIONS: Portuguese version of Inflammatory Bowel Disease Questionnaire is a valid and reproducible instrument which can be used to evaluate the quality of life of Brazilian inflammatory bowel diseases patients.

Adult↗

PubMed2004

T-cell-mediated signalling in immune, inflammatory and angiogenic processes: the cascade of events leading to inflammatory diseases.

In the last decade, the understanding of the molecular mechanisms of regulation of the inflammatory process in chronic inflammatory diseases has moved remarkably forward. Recent evidence in various fields has consistently indicated that T-cells play a key role in initiating and perpetuating inflammation, not only via the production of soluble mediators but also via cell/cell contact interactions with a variety of cell types through membrane receptors and their ligands. Signalling through CD40 and CD40 ligand is a versatile pathway that is potently involved in all these processes. In this article, we review how T-cells become activated by dendritic cells or inflammatory cytokines, and how these T-cells activate, in turn, monocytes/macrophages, endothelial cells, smooth muscle cells and fibroblasts to produce pro-inflammatory cytokines (tumour necrosis factor alpha, interleukin-6), chemokines (interleukin-8, monocyte chemotactic protein-1), tissue factor, the main initiator of the coagulation cascade in vivo, and finally matrix metalloproteinases, responsible for tissue destruction. Moreover, we discuss how CD40 ligand at inflammatory sites stimulates fibroblasts and tissue monocyte/macrophage production of VEGF, leading to angiogenesis, which promotes and maintains the chronic inflammatory process. This cascade of events is discussed in the context of disease initiation/progression, with particular reference to atherosclerosis and rheumatoid arthritis, and to potential novel therapeutic targets for their treatment.

Animals↗

PubMed1999

A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype.

Inflammatory breast cancer is a rapidly growing, distinct form of locally advanced breast cancer that carries a guarded prognosis. To identify the genes that contribute to this aggressive phenotype, we compared under- and overexpressed sequences in an inflammatory breast tumor cell line with those of actively replicating normal human mammary epithelial cell lines using differential display. Of the 17 transcripts isolated and characterized from these experiments, overexpression of RhoC GTPase and loss of expression of a novel gene on 6q22, LIBC (lost in inflammatory breast cancer), were highly correlated (P<0.0095 and P<0.0013, respectively) with the inflammatory phenotype when a panel of archival inflammatory breast cancers was compared with noninflammatory stage III breast cancers by in situ hybridization. This study suggests two new molecular markers specific for inflammatory breast cancer.

Amino Acid Sequence↗

PubMed1992

Comparative studies on inflammatory reactions induced by non-immunological and immunological stimuli in an air pouch and in a carboxymethyl cellulose (CMC)-induced inflammatory pouch.

Inflammatory reactions were compared in the air pouch and the CMC pouch. Inflammation was induced by injection of CMC as a non-specific irritant, lipopolysaccharide (LPS) as an activator of macrophages, and methylated bovine serum albumin (m-BSA) as an inducer of delayed type hypersensitivity. There was no prominent difference in the inflammatory reactions following injection of 2% CMC solution into a 4-day-old air pouch and a 3-day-old CMC pouch. On the other hand, injection of 4 ml of 100 ng/ml LPS into each of the pouches enhanced the inflammatory reactions in the CMC pouch several-fold compared with those in the air pouch. A similar tendency was found in the case of an injection of 1 ml of 1 mg/ml m-BSA in rats sensitized with 1 mg of m-BSA. The enhanced inflammatory reactions induced by the injection of LPS or m-BSA were inhibited by dexamethasone, but not by indomethacin. These results indicate that the enhanced inflammatory reactions induced by CMC are related to lining tissue formation, which was a common characteristic in both pouches. Enhanced inflammatory reactions following injection of LPS and m-BSA were related to the activation of macrophages and newly formed blood vessels, which were not characteristic features in the air pouch, but were in the CMC pouch, in addition to the lining tissue. Cyclo-oxygenase products were not associated with the reactions.

Air Sacs↗

PubMedDate not supplied

Different pro-inflammatory and immunogenic potentials of Propionibacterium acnes and Staphylococcus epidermidis: implications for chronic inflammatory acne.

INTRODUCTION: Propionibacterium acnes (PA) and Staphyloccocus epidermidis (SE) are two major bacterial strains isolated from acne lesions. Nevertheless, only PA seems to be implicated in the pathogenesis of inflammatory acne vulgaris. Evidence for this, however, remains indirect and the precise role of PA in inflammatory acne is still a matter for conjecture. The aim of this study was to compare some pro-inflammatory and adjuvant properties of PA and SE. MATERIAL/METHODS: To determine some of the pathogenic, immunostimulatory, and pro-inflammatory proper of PA and SE, two experimental models of inflammation were used. In vivo; chronic inflammation was induced by intradermal injection of living bacteria into the ear. In vitro; peritoneal macrophages elicited by the bacteria were examined for their ability to generate reactive oxygen species (ROS), nitric oxide (NO), and cytokines. RESULTS: PA, but not SE, evoked mild local inflammation of infected ears. Macrophages elicited with PA produced more tumor necrosis factor alpha and interleukin IL-12 than those induced with SE, while SE was a stronger inducer of IL-10 production. Both bacteria equally induced the generation of NO and ROS. In contrast, only PA showed adjuvant proper-ties. CONCLUSIONS: The results of these studies indicate that SE, in contrast to PA, does not exert pro-inflammatory properties. Thus it is unlikely that SE may be implicated in the pathogenesis of inflammatory acne vulgaris.

Acne Vulgaris↗

PubMed1996

In vivo fate of the inflammatory macrophage during the resolution of inflammation: inflammatory macrophages do not die locally, but emigrate to the draining lymph nodes.

The resolution of acute inflammation requires bulk clearance of extravasated inflammatory cells in an ordered manner. Neutrophils undergo apoptosis and are ingested by macrophages (M psi) via a novel recognition mechanism that fails to provoke proinflammatory responses. Thereafter, the fate of inflammatory M psi themselves remains unclear. We investigated this in vivo, developing a semiallogeneic adoptive transfer system to track the fate of inflammatory M psi in a murine model of resolving peritonitis. Fluorescently labeled M psi from H-2k/d mice were transferred into the peritoneal cavity of H-2k mice at the same stage of resolving inflammation as the donor mice. Dual color flow cytometry permitted discrimination among donor cells, recipient cells, and donor cells that had been phagocytosed by recipient M psi. Despite the absence of significant local phagocytosis, the number of transferred M psi free in the peritoneum of recipient mice declined rapidly, being undetectable by 96 h. These data suggest that inflammatory M psi normally emigrate rapidly from the peritoneal cavity during the resolution of inflammation, contrasting with resident M psi, which persist in the noninflamed peritoneum for weeks. Accordingly, labeled nonphagocytosed cells were detected in the draining lymph nodes, but not in a variety of other tissues. Thus, unlike the polymorphonuclear leukocyte, which dies by apoptosis and is ingested by M psi, the inflammatory M psi itself does not die locally. Having performed its acute inflammatory and scavenging roles, it emigrates in a nonrandom fashion to the draining lymph node, where it may play an important part in the presentation of Ags from the inflamed site.

Adoptive Transfer↗

PubMed1995

A study of the novel anti-inflammatory agent florifenine topical anti-inflammatory activity and influence on arachidonic acid metabolism and neutrophil functions.

We have evaluated the effects of the novel anti-inflammatory agent florifenine, 2-(1-Pyrrolidinyl)ethyl N-[7-(trifluoromethyl)-4-quinolyl]anthranilate, on topical inflammation in mice, free radical-mediated reactions, arachidonic acid metabolism and some neutrophil functions. Topical administration of florifenine produced dose-related anti-inflammatory activity in 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear oedema and with a lower potency, in the response induced by arachidonic acid (AA). Florifenine also inhibited neutrophil migration and PGE2 content in the inflammed ears. In human whole blood, florifenine was a potent and selective inhibitor of TXB2 generation. This anti-inflammatory agent did not exert antioxidant effects but inhibited elastase release in human neutrophils without affecting superoxide anion generation. Florifenine administration to mice dose-dependently inhibited leukocyte migration and PGE2 levels in the air pouch inflammation induced by zymosan. These results demonstrate the topical anti-inflammatory activity of florifenine and provide a basis for understanding the mechanisms involved in the inhibitory effects of this agent on inflammatory responses.

Administration, Topical↗

PubMed2025

Genetic predisposition to systemic inflammatory proteins is causally associated with inflammatory bowel disease: Insights from multi-omics association study and single-cell RNA-sequencing analysis.

Systemic inflammatory proteins have been reported to be related to inflammatory bowel disease (IBD) in previous observational research. However, their causal links remain obscure. Herein, we performed a Mendelian randomization (MR) analysis to analyze the causality between systemic inflammatory proteins and IBD. Genetic variants related to systemic inflammatory proteins were extracted from a meta-analysis of genome-wide association study (GWAS) data of 8293 European participants. Summary statistics of IBD diverse subtypes were obtained from the international IBD genetic consortium (IIBDGC). We conducted multi-omics method and MR study to detect the causal links through integrating GWAS and protein quantity trait loci (pQTL) data. Inverse variance weighted (IVW) approach was utilized as the dominated analysis method. Moreover, complementary approaches such as MR-Egger intercept test, Cochran Q test and leave-one-out analysis were utilized to validate pleiotropy and heterogeneity. Finally, single-cell RNA-sequencing analysis was performed to detect the expression of significant genes. For IBD, IVW estimates suggested that genetically predicted IL-10 and IL-13 were suggestively associated with an elevated risk of IBD (IL-10: OR: 1.12, 95% CI: 1.00-1.24, P = .04; IL-13: OR: 1.09, 95% CI: 1.01-1.18, P = .023), while CXCL10 was suggestively linked to a lower risk of IBD (CXCL10: OR: 0.90, 95% CI: 0.82-0.99, P = .037). For Crohn disease (CD), the IVW approach provided evidence to sustain that genetically determined IL-13 and CCL3 had a suggestive association with a higher risk of CD (IL-13: OR: 1.13, 95% CI: 1.02-1.26, P = .023; CCL3: OR: 1.22, 95% CI: 1.03-1.45, P = .018). Sensitivity analysis did not explore any heterogeneity and pleiotropy. Our findings supported the causal relationships between 4 specific inflammatory proteins (IL-10, IL-13, CXCL10, and CCL3) and the risk of IBD and CD, thereby providing promising biomarkers of various subtypes stratification and new insights for the prevention and therapeutic target of IBD.

Humans↗

PubMed2005

Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory agents in the treatment of neurodegenerative disease.

Inflammation is characteristic of a broad spectrum of neurodegenerative diseases. These include Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases, amyotrophic lateral sclerosis, all of the tauopathies, multiple sclerosis and many other less common conditions. Morphologically, the level of inflammation is determined by the concentration and degree of activation of microglial cells. Biochemically, it is judged by the presence of a spectrum of inflammatory mediators. Epidemiological evidence indicates that anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs) have a sparing effect on AD and PD indicating that inflammation exacerbates the pathology in these diseases. NSAIDs are protective in transgenic animal models of AD, providing further evidence of the negative consequences of inflammation. Here we describe an in vitro model, which was used to study the protective effects of NSAIDs in AD. This model is based on neuronal cell killing by stimulated microglia or microglia-like cells. In this model NSAIDs show protective effects at a therapeutically relevant level, which is in the low micromolar range. There are reports suggesting that NSAIDs act independently of cyclooxygenase (COX) inhibition, but only at higher doses. Classical NSAIDs are still the most logical choice for agents that will slow the progression or delay the onset of AD and other neurodegenerative diseases despite failures of naproxen, celecoxib and rofecoxib in AD clinical trials. Several other classes of anti-inflammatory drugs have been identified as potentially beneficial in this and similar assay systems. Therefore combination therapy with other anti-inflammatory agents that work through different mechanisms of action might prove to be a superior therapeutic strategy.

Alzheimer Disease↗

PubMed2002

Continuous milrinone infusion during preoperative anti-inflammatory therapy in inflammatory aortic aneurysm complicating severe congestive heart failure.

We report a 48-year-old man with inflammatory aortic aneurysm in the ascending aorta complicating severe heart failure due to massive aortic regurgitation. Continuous intravenous milrinone infusion was highly effective in reducing pulmonary arterial pressure and improving subjective symptoms during preoperative anti-inflammatory corticosteroid therapy over 7 weeks without any adverse effects or tolerance. Bentall's operation with a valved conduit was successfully performed after complete stabilization of inflammatory markers, and then milrinone was tapered off uneventfully. We consider that continuous milrinone infusion may be suitable for patients with surgically correctable inflammatory cardiovascular diseases complicating severe heart failure in whom maintenance of optimal hemodynamics is necessary for several weeks during preoperative anti-inflammatory corticosteroid therapy.

Adrenal Cortex Hormones↗

PubMed1983

Decrease of urinary prostaglandin E2 and prostaglandin F2 alpha excretion by nonsteroidal anti-inflammatory drugs in rats. Relationship to anti-inflammatory activity.

An analytical method for measuring in vivo inhibition of prostaglandin (PG) synthesis by nonsteroidal anti-inflammatory drugs was developed for estimation of urinary prostaglandin levels in rats. Drugs were administered orally to rats (Wistar, male, 200-250 g), and water (2.5 ml/100 g body weight) was given 1 hr after drug administration to yield a constant volume of urine. Urine was collected for 4 hr after drug administration, and urinary PGE2 and PGF2 alpha were determined by radioimmunoassay. The urine volume in the 4-hr period was 5.0 +/- 0.30 ml per rat, and prostaglandin contents in the 4-hr urine were 4.56 +/- 0.56 ng PGE2 and 1.31 +/- 0.24 ng PGF2 alpha per rat in the no-drug control group. Administration of nonsteroidal anti-inflammatory drugs decreased the urinary PGE2 and PGF2 alpha dose dependently. The activities of ten typical nonsteroidal anti-inflammatory drugs in reducing urinary PGE2 excretion were compared with their anti-inflammatory activities in rats. A close correlation (r = 0.98, P less than 0.001) between the dose required for 50% reduction of urinary PGE2 excretion and the dose required for 50% inhibition of carrageenin edema was found for each drug. These drugs were also tested for their inhibitory effects on PGE2 biosynthesis in a cultured system of mouse 3T6 fibroblast cells and on prostaglandin synthesizing system in bovine seminal vesicle microsomes. No close correlation was observed between anti-inflammatory activities and inhibition of prostaglandin biosynthesis in vitro.

Animals↗

PubMed1985

Role of ceruloplasmin in inflammation: increased serum ceruloplasmin levels during inflammatory conditions and its possible relationship with anti-inflammatory agents.

Serum ceruloplasmin (CPN) levels under different types of acute and chronic experimentally-induced inflammatory conditions in rats and the effect of anti-inflammatory drugs viz. oxyphenylbutazone and hydrocortisone on serum CPN levels were investigated. Significant increase of serum CPN levels was observed in all experimental animal models with induced inflammatory conditions. Treatment with oxyphenylbutazone and hydrocortisone failed to inhibit the raised serum CPN levels. The concurrent increase of serum CPN level during induced inflammatory conditions suggest the involvement of serum CPN as one of the body's inbuilt defensive mechanism against noxious responses or inflammation. It is suggested that the increased serum CPN levels may be a complimentary factor associated with inflammatory conditions.

Animals↗

PubMed2006

Inhibition of the pro-inflammatory mediators' production and anti-inflammatory effect of the iridoid scrovalentinoside.

We have studied scrovalentinoside, an iridoid with anti-inflammatory properties isolated from Scrophularia auriculata ssp. pseudoauriculata, as an anti-inflammatory agent in different experimental models of delayed-type hypersensitivity. We found that scrovalentinoside reduced the edema induced by oxazolone at 0.5 mg/ear and sheep red blood cells at 10 mg/kg. The observed effect occurred during the last phase or inflammatory response; during the earlier phase or induction of the delayed-type hypersensitivity reaction, no significant activity was noted. Thus, scrovalentinoside reduced both the edema and cell infiltration in vivo and reduced lymphocyte proliferation in vitro, affecting the cycle principally during the first 48 h. Whereas cells stimulated with phytohemagglutinin changed from the G(0)/G(1) phase to the S and G(2)/M phases, when these same cells were treated with scrovalentinoside (100 microM), they remained in the G(0)/G(1) phase. Finally, scrovalentinoside inhibited the production of the pro-inflammatory mediators' TNF-alpha, IFN-gamma, IL-1beta, IL-2, IL-4, LTB(4), and NO, but had no effect on the production of the anti-inflammatory cytokine IL-10.

Animals↗

PubMed2001

Macrophage inflammatory protein-1alpha relates to the recruitment of inflammatory cells in myosin-induced autoimmune myocarditis in rats.

In experimental autoimmune myocarditis (EAM) there is a characteristic initial focal inflammatory response in the myocardium, induced mainly by CD4(+) T cells and macrophages, which leads to massive myocardial damage. Macrophage inflammatory protein-1alpha (MIP-1alpha) induces chemotaxis in lymphocytes, eosinophils, basophils, and macrophages. We assessed the potential role of MIP-1alpha in the pathogenesis of EAM in rats immunized with porcine myosin. Following immunization, the levels of MIP-1alpha mRNA in EAM showed an increase on Day 11 and peaked on Day 17. MIP-1alpha-positive cells were predominantly immunoreactive to OX6 antibody (dendritic cells) and ED2 antibody (resident macrophages) by Day 14. Marked cellular infiltration was seen on Day 17 with the major population of MIP-1alpha-positive cells also positive for ED1 (inflammatory macrophages). We then examined the association of MIP-1alpha with the development of myocardial inflammation. Rats were divided into three groups: Group A consisted of EAM rats (n = 10); Group B consisted of EAM rats treated with anti-MIP-1alpha (1 mg/kg) on Days 11, 13, and 15, before the onset of initial inflammation (n = 5); and Group C consisted of EAM rats treated with anti-MIP-1alpha from the start of the initial inflammation on Days 14, 16, and 18 (n = 5). Rats were euthanized on Day 21 and three transverse sections of the heart were prepared to determine the percentage of the area affected by inflammatory lesions. This area of inflammation was significantly smaller in Group B (27 +/- 4%) than in Groups A (51 +/- 6%) or C (50 +/- 6%) (p < 0.01), indicating that the administration of antibody before the initiation of inflammation, in part, will inhibit myocardial inflammation. These data suggest that MIP-1alpha may play an important role in the recruitment of inflammatory cells in the early stages of EAM.

Animals↗