Associations between interleukin 18 gene polymorphisms and susceptibility to vasculitis: A meta-analysis.

Interleukin 18 (IL18), a pro-inflammatory cytokine, affects the development and progress of vasculitis. The production, expression, and function of this cytokine are affected by polymorphisms of promoter region of the IL18 gene. In this study, a meta-analysis of the associations between several IL18 polymorphisms and susceptibility to vasculitis was performed. Published literature from PubMed and Embase were retrieved. In total, nine studies comprising 1006 patients with vasculitis and 1499 controls combined, and the investigating the rs187238, rs194618, and rs360719 polymorphisms of the promoter region of the IL18 gene, were included in the meta-analysis. Pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated with fixed-effects model or random-effects model. The recessive model of the rs194618 polymorphism was found to be significantly associated with a high susceptibility to vasculitis (OR = 1.54, 95% CI = 1.02-2.33, P = 0.04), especially in the Mongoloid race, where the A allele of rs194618 was associated with a low risk of the disease (OR = 0.77, 95% CI = 0.62-0.95, P = 0.01). By contrast, the rs187238 and rs360719 polymorphisms were not associated with this inflammatory condition. This meta-analysis showed that some IL18 polymorphisms are associated with susceptibility to vasculitis. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 203-211).

The Association of Vitamin D Status with Dyslipidaemia and Biomarkers of Endothelial Cell Activation in Older Australians.

BACKGROUND/AIMS: Vitamin D has been investigated for many non-skeletal effects. The objective of this study was to determine whether circulating lipids, systemic inflammation, and biomarkers of endothelial cell activation varied with the vitamin D status of older Australians. METHODS: One hundred and one participants were proportionately and randomly sampled across tertiles of 25 hydroxy vitamin D (25(OH)D) from a larger cohort of free living older adults (T1 median = 97; T2 median = 74.5; T3 median = 56.8 nmol/L). Overnight fasting blood samples were assayed for 25(OH)D, parathyroid hormone (PTH), insulin, triacylglycerol (TAG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). Markers of systemic inflammation (high sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α)) and endothelial activation (hepatocyte growth factor (HGF), P-selectin and soluble vascular cell adhesion molecule (sVCAM), soluble intracellular adhesion molecule (sICAM)) were determined. A general linear model multivariate analysis with a backward elimination procedure was performed. RESULTS: Eighty-three participants (48 women, 35 men), aged 65 ± 7.7 years, BMI 28 ± 4.5 kg/m², with complete data were analyzed. The final parsimonious model controlled for age, gender, BMI, and McAuley's index, but excluded season, medications, and PTH. There were significant differences across 25(OH)D tertiles in TC (T1 < T3, p = 0.003; T2 < T3, p = 0.001), LDL-C (T1 < T3, p = 0.005; T2 < T3, p = 0.001), TAG (T2 < T3, p = 0.026), HGF (T1 > T3, p = 0.009) and sVCAM (T1 > T3, P = 0.04). CONCLUSIONS: Higher vitamin D status may protect the endothelium through reduced dyslipidaemia and increased HGF.

Associations between interleukin-1 polymorphisms and susceptibility to vasculitis: a meta-analysis.

OBJECTIVE: The objective of this study was to determine whether interleukin-1 (IL-1) polymorphisms are associated with susceptibility to vasculitis. METHODS: A meta-analysis was conducted to investigate possible associations between IL-1A, IL-1B, and IL-1 receptor antagonist (IL1RN) polymorphisms and vasculitis. RESULTS: A total of 17 studies involving 1384 vasculitis cases [Behçet's disease (BD), IgA vasculitis, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), Kawasaki disease (KD), giant cell arteritis, and Takayasu's arteritis] and 2710 controls were included in the meta-analysis. This analysis showed an association between BD and the TT + TC genotypes of the IL-1A-889 C/T polymorphism in the entire study population [odds ratio (OR) = 0.623, 95 % CI = 0.395-0.981, p = 0.045), and a trend toward an association in a Turkish population (OR = 0.578, 95 % CI = 0.331-1.010, p = 0.054). A meta-analysis of the IL1RN polymorphism revealed no association with vasculitis in all study subjects (OR for IL1RN*2 = 0.904, 95 % CI = 0.626-1.304, p = 0.588). However, stratification by ethnicity revealed a significant association between the IL1RN*2 allele and vasculitis including AAV, BD, KD in Asians (OR = 2.393, 95 % CI = 1.429-4.006, p = 0.001), but not in Caucasian and Turkish populations (OR = 0.776, 95 % CI = 0.487-1.238, p = 0.288; OR = 0.914, 95 % CI = 0.667-1.252, p = 0.576, respectively). No association was found between vasculitis and the IL-1B-511 C/T polymorphism, or the IL-1B+3953 C/T polymorphism. CONCLUSIONS: This meta-analysis suggests that the IL-1A-889 C/T polymorphism is associated with susceptibility to BD, and that the IL1RN*2 allele is associated with susceptibility to vasculitis including AAV, BD, and KD in Asians.

Diverging trajectory patterns of systemic versus vascular inflammation over age in healthy Caucasians and African-Americans.

OBJECTIVE: Age and inflammation are risk factors for cardiovascular disease but the impact of inflammation on cardiovascular risk across the lifespan is not understood. We investigated whether an inflammatory burden is modulated by age in healthy subjects. METHODS: Caucasian and African-American families were recruited from the general population (age range: 6-74 years, n = 267). Systemic inflammation was assessed by C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, haptoglobin and α-acid glycoprotein, and vascular inflammation was assessed by pentraxin-3 (PTX-3), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM). To collectively assess systemic or vascular factors across the age spectrum, a composite z-score for each marker category was calculated. RESULTS: There was a contrasting pattern in systemic versus vascular inflammatory burden over age with an increase in systemic but a decrease in vascular markers in both ethnic groups. The results remained unchanged after adjustments for the covariates and covariance. When looking at individual markers to examine which markers are most contributing factors to the composite scores, CRP and SAA were significantly and positively associated with age, while PTX-3 and sVCAM were significantly and negatively associated with age in both ethnic groups. CONCLUSIONS: The composite z-score for systemic inflammation increased with age, while the composite z-score for vascular inflammation declined with age, irrespective of ethnicity. The findings illustrate a regulatory relationship between age and inflammation, and suggest that a perceived elevation of vascular markers among the very young may be an indication of physiological changes rather than reflecting a disease process.

Vascular endothelial growth factor gene polymorphisms and vasculitis susceptibility: A meta-analysis.

OBJECTIVE: The aim of this study was to explore whether vascular endothelial growth factor (VEGF) polymorphisms are associated with susceptibility to vasculitis. METHODS: Meta-analyses were conducted on the associations between the -634 C/G, +936 C/T, -1154 A/G, and -2578 A/C polymorphisms of VEGF and vasculitis. RESULTS: Eight studies on VEGF polymorphisms and vasculitis involving 2740 subjects (vasculitis 834, controls 1906) were included in this meta-analysis. The meta-analysis showed no association between vasculitis and the VEGF -634 C allele (OR=1.161, 95% CI=0.921-1.464, p=0.207) among study subjects. Meta-analysis showed no association between vasculitis and the VEGF+936 T allele (OR=1.121, 95% CI=0.905-1.390, p=0.295). However, stratification by ethnicity indicated a significant association between the VEGF+936 T allele and vasculitis in Europeans, but not in Asians (OR=1.486, 95% CI=1.038-2.128, p=0.030; OR=0.958, 95% CI=0.773-1.253, p=0.755). Meta-analysis showed no association between vasculitis and the VEGF -1154 A/G and 2578 A/C polymorphisms. CONCLUSIONS: This meta-analysis suggests that the VEGF+936 T allele is associated with susceptibility to vasculitis in Europeans, but not in Asians.

Antiphospholipid syndrome in a young Nigerian girl presenting with gangrenous toes.

We report on a 21-year-old Nigerian girl with toe gangrene, which is one of the most unlikely forms of presentation of antiphospholipid syndrome among Africans. The essence of this case report is to raise awareness that, although antiphospholipid syndrome typically presents in Africans in association with a pregnancy-related event or a neuropathology, it should be considered as a differential diagnosis in all African patients with unexplained vasculitis. A high index of suspicion and early treatment will prevent toe amputations and reduce mortality rates.

Epidemiology of vasculitides: differences between Japan, Europe and North America.

The epidemiology of systemic vasculitides differs between Japan, Europe and North America. Takayasu's arteritis occurs frequently in Japan, unlike giant cell arteritis. A collaborative international study comparing the epidemiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis between Japan and the United Kingdom (UK) demonstrated that microscopic polyangiitis and myeloperoxidase-ANCA were more common in Japan, whereas granulomatosis with polyangiitis and pronase 3-ANCA were more common in the UK. These differences may be attributed to differences in latitude and genetic backgrounds. These findings provide useful information on the aetiology and pathogenesis of primary systemic vasculitides in various geographical regions.

Effect of race/ethnicity on risk, presentation and course of connective tissue diseases and primary systemic vasculitides.

PURPOSE OF REVIEW: Understanding the effects of race/ethnicity on the risk and expression of systemic rheumatic diseases has potential clinical implications and provides insight into their etiopathogeneses. This review summarizes knowledge of the effects of race/ethnicity on the following nine conditions: antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), Behçet's disease, dermatomyositis/polymyositis, Henoch-Schönlein purpura, Kawasaki disease, large-vessel vasculitis (LVV), primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). RECENT FINDINGS: Distinct racial/ethnic patterns have emerged for most of the conditions considered here. Areas of progress include the finding that the two AAVs, granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis, exhibit distinct racial/ethnic susceptibilities in disease risk. In addition, nonwhites, with known high risk of SLE and SSc, may also be at a high risk for pSS and have more severe disease. Evidence is accumulating that nonwhites are rarely affected by the LVV giant-cell arteritis. Race/ethnicity-specific genetic risk factors were recently detected for GPA. SUMMARY: Epidemiologic data have allowed discerning the racial/ethnic profiles for many of the considered systemic rheumatic conditions. Future challenges will be to unravel the genetic, environmental and/or socio-econonomic determinants of the observed racial/ethnic disparities. More research is needed to clarify the impact of race/ethnicity on the AAV Churg-Strauss syndrome, dermatomyositis/polymyositis and Takayasu arteritis.

Polymyalgia rheumatica and the risk of stroke: a three-year follow-up study.

BACKGROUND: Polymyalgia rheumatica (PMR) is a relatively common rheumatic disease, particularly in the elderly. Vasculitis is associated with PMR and theoretically makes such patients susceptible to vascular events such as stroke. This study aims to explore the frequency and risk of stroke among patients with PMR through a population-based case-controlled study. METHODS: The study included 781 patients with PMR from the Taiwan Longitudinal Health Insurance Database between 2001 and 2005. We randomly extracted 3,905 other patients, matched with the study group in terms of sex and age, as a control population. Each subject was individually tracked for a three-year period to identify those who had strokes. Stratified Cox proportional hazard regression was employed to evaluate the risk of stroke, after adjusting for socio-demographic characteristics and comorbidities. RESULTS: We found that 386 out of 4,686 sampled patients (8.24%) had stroke during the three-year follow-up period, including 113 patients with PMR (14.47% of the PMR group) and 273 controls (6.98% of the control group). The stratified Cox proportional hazard regression showed that the adjusted hazard ratio of stroke for patients with PMR was 2.09 times that of controls (95% CI = 1.63-2.66, p <0.001), after adjusting for socio-demographic characteristics and comorbidities. CONCLUSIONS: PMR was associated with a significantly higher risk of stroke in the three-year follow-up period. Physicians should be aware of this potential association in clinical settings.

Frosted branch angiitis, presumably related to dermatomyositis.

PURPOSE: To report the first case of frosted branch angiitis associated with dermatomyositis in a Korean woman. METHODS: Case report. RESULTS: A 42-year-old woman with history of dermatomyositis presented with unilateral decreased visual acuity. Fundus examination showed findings consistent with frosted branch angiitis. After 1 month of oral prednisolone, the patient made significant visual recovery with near complete resolution of vascular sheathing. CONCLUSIONS: To the best of the authors' knowledge, this is the first case of frosted branch angiitis associated with dermatomyositis. Dermatomyositis should be considered in the differential diagnosis of patients presenting with frosted branch angiitis.

Inflammation and descending thoracic aortic calcification as detected by computed tomography: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Inflammation is related to many stages of atherosclerosis, and inflammatory markers have been associated with both atherosclerosis and future cardiovascular events. Descending thoracic aortic calcification (DTAC) is a manifestation of atherosclerosis, however, no previous study has examined the relationship of inflammatory markers and DTAC as detected by computed tomography (CT) in a large study. We examined whether C-reactive protein (CRP) and interleukin-6 (IL-6) are independently associated with DTAC. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study that includes 6814 women and men ages 45-84 years old, all free of baseline cardiovascular disease. The inflammation markers CRP and IL-6, and DTAC by CT, quantified by Agatston score, were measured at baseline in all participants. RESULTS: We studied 6613 participants with complete data (3112 men, 3501 women, mean age 62+/-10 years). The prevalence of DTAC was 27%. Participants with DTAC had significantly higher levels of both CRP and IL-6. After adjustment for baseline risk factors, CRP was not correlated with presence or severity of DTAC (Adjusted RR per S.D., 1.01; 95% confidence intervals 0.97; 1.05) while IL-6 associations remained significant (adjusted RR per S.D., 1.07; 95% confidence intervals 1.02; 1.14). CONCLUSIONS: IL-6, a systemic inflammatory marker, is related to the presence and extent of DTAC. Further studies are needed to evaluate the interaction between DTAC and inflammation markers as predictors of future cardiovascular events.

An international matched cohort study of the contribution of metabolic impairments to subclinical atherosclerosis in United Kingdom and Jamaican African-Caribbeans.

BACKGROUND: A gradient of increased vascular risk exists across the African diaspora. We hypothesised that increased insulin resistance with environmental transition contributes to this risk. METHODS: The study was undertaken in 73 healthy African-Caribbeans in the UK and 151 age and sex matched African-Caribbeans in Jamaica. Body mass index (BMI), fasting insulin, insulin resistance, carotid intima media thickness (CIMT) and endothelium dependent vasodilatation (EDV) were compared. CIMT was measured ultrasonographically in the distal 1cm of both common carotid arteries. EDV was measured the absolute change from baseline in the Reflection index (RI) of the digital volume pulse during intravenous infusion of albuterol (DeltaRI(ALB)). RESULTS: UK African-Caribbeans had greater CIMT (mean difference 0.124 [95% C.I. 0.075-0.173] mm, p<0.0001) and decreased EDV (mean difference in DeltaRI(ALB) 5.1 [95% C.I. 2.5-7.6] percentage points, p<0.0001). This was associated with higher insulin concentrations (mean difference 1.6 [95% C.I. 1.3-4.1] microU/mL, p=0.038) and greater HOMA score (2.8 versus 2.0; p=0.035) despite no significant differences in BMI (28.8 versus 27.6; p=0.168) or the waist to hip ratio (0.86 versus 0.85; p=0.188). HOMA scores correlated positively with CIMT (r=0.35, p=0.01) and negatively with DeltaRI(ALB) (r=-0.17; p=0.02) in UK, but not in Jamaican, African-Caribbeans. A significant interaction was seen between HOMA and UK domicile for CIMT (p<0.0001) and between fasting insulin and UK domicile for DeltaRI(ALB) (p<0.0001). CONCLUSIONS: Increased insulin resistance, associated with living in a nutritionally enriched environment, may contribute to early subclinical atherosclerosis in UK African-Caribbeans.

A comparative study of the diagnostic accuracy of ELISA systems for the detection of anti-neutrophil cytoplasm antibodies available in Japan and Europe.

OBJECTIVES: Primary systemic vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA) differs in its frequency and clinical expression between Japan and Europe. We sought to ascertain whether such differences arise from the performance of enzyme-linked immunosorbent assays (ELISAs) for ANCA. METHODS: Plasma samples from 64 consecutive Japanese patients with a clinical and histological diagnosis of primary systemic vasculitis including microscopic polyangiitis (MPA; n=52), Churg-Strauss syndrome (CSS; n=1), and Wegener's granulomatosis (WG; n=11), or those from disease controls with non-vasculitic glomerulonephritis (n=54) and healthy controls (n=55) were tested for the presence of myeloperoxidase (MPO) by ELISAs available in Japan (Nipro and MBL) and compared with those in Europe (Wieslab). The sensitivity and specificity were calculated for each ELISA, and its diagnostic performance was assessed by receiver operating characteristic curve analysis. RESULTS: The sensitivity and specificity of either MPO-ANCA assays for a diagnosis of MPA were 90.4% and 98.2% (Nipro), 88.2% and 96.3% (MBL), and 86.5% and 99.1% (Wieslab). The overall diagnostic performance, assessed as the area under curve of the MPO-ANCA ELISAs for MPA were 0.946+/-0.022 (Nipro), 0.970+/-0.017 (MBL), and 0.971+/-0.017 (Wieslab), while that of PR3-ANCA ELISAs for WG were 0.986+/-0.025 (Nipro), 0.993+/-0.017 (MBL), and 0.916+/-0.059 (Wieslab). CONCLUSIONS: The MPO-ANCA ELISAs commercially available in Japan exhibited high sensitivity and specificity for the diagnosis of ANCA-associated vasculitides and provided similar diagnostic value to those in Europe. These results facilitate further international comparison of ANCA-associated vasculitides between Japanese and European populations.

Hepatitis B-associated vasculitis in Alaska Natives: viral genotype, clinical and serologic outcome.

BACKGROUND: The highest incidence of hepatitis B virus (HBV)-associated vasculitis in the world has been reported in Alaska Natives. We examined the incidence of HBV-associated vasculitis before and after mass HBV vaccine immunization and the association between HBV genotype and vasculitis in a population-based cohort study in Alaska natives chronically infected with HBV. METHODS: Genotyping was performed in vasculitis cases and 644 hepatitis B-positive controls without vasculitis using polymerase chain reaction and sequencing of the S gene. Occurrence of HBV vasculitis from 1974 to 2004 was calculated. HBV vasculitis patients and controls were also tested for basal core promoter and precore mutations. RESULTS: Fifteen cases of HBV-associated vasculitis were identified: 13 (86%) had genotype D and one each genotype A and F. Genotype D was more commonly found in patients with vasculitis than controls [odd ratio (OR)=5.9, confidence interval (95% CI) 1.2, 21.8; P<0.015). CONCLUSIONS: HBV-associated vasculitis was associated with genotype D.

Clinical [corrected] and pathological characteristics of Chinese patients with antineutrophil cytoplasmic autoantibody associated systemic vasculitides: a study of 426 patients from a single centre.

BACKGROUND: Antineutrophil cytoplasmic autoantibodies (ANCA) are serological markers of ANCA associated systemic vasculitides (AASV), which is one of the most common multisystem autoimmune diseases. Features of Chinese patients with AASV have not been fully investigated. OBJECTIVE: To analyse the clinical and pathological characteristics of Chinese patients with AASV. METHODS: 426 Chinese patients with AASV diagnosed in the past eight years were retrospectively studied and their clinical and pathological data were analysed. RESULTS: Of the 426 patients, 87 (20.4%) were Wegener's granulomatosis, 337 (79.1%) were microscopic polyangiitis and two (0.5%) were Churg-Strauss syndrome. Only 201 of 426 (47.2%) patients were diagnosed within three months. Clinically, the patients had multisystem involvement. Altogether 371 of 426 (87.1%) had kidney involvement and 260 of 426 (61.0%) had lung involvement. The prevalences of renal involvement and fatigue were significantly higher in patients with MPO-ANCA than that in patients with PR3-ANCA; the prevalences of ophthalmic, nasal involvement, rash, and arthragia were significantly higher in patients with PR3-ANCA than those in patients with MPO-ANCA. The one and five year death rates were 13.1% and 22.4%, respectively. The percentage of patients progressing to end stage renal disease at one and five years was 15.9% and 27.1%, respectively. CONCLUSIONS: AASV is not a rare autoimmune disease in Chinese people. Kidney and lung were the most vulnerable organs. For patients with multiorgan damage, an ANCA test should be performed to make an early diagnosis and to start treatment in time.

Incidence of Henoch-Schönlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins.

BACKGROUND: The frequency and ethnic variation of Henoch-Schönlein purpura, Kawasaki disease, and rarer vasculitides during childhood are not well characterised. Our aim was to ascertain the incidence and ethnic distribution of these conditions in children resident in a region of the UK with a diverse ethnic mix. METHODS: 1.1 million children younger than age 17 years live in the West Midlands. Between Sept 1, 1996, and Aug 31, 1999, we surveyed this population with monthly questionnaires sent to 321 consultants, a single questionnaire sent to 2860 family doctors, and review of 406 case notes with diagnostic codes for vasculitis. We included in the analyses children who fulfilled established criteria for vasculitis with disease onset during the study, and calculated incidence rates from population rates derived from the census of 1991. FINDINGS: We identified 586 new instances of vasculitis and connective tissue disease. The estimated annual incidence of Henoch-Schönlein purpura was 20.4 per 100000, and was highest between the ages of 4 years and 6 years (70.3 per 100000). The estimated annual incidence of Kawasaki disease was 5.5 per 100000 in children younger than 5 years, and was highest in Indian subcontinent Asian children (14.6 per 100000). Indian subcontinent Asian and black children had the highest incidence of systemic lupus erythematosus, juvenile dermatomyositis, and other primary systemic vasculitides. INTERPRETATION: Childhood Henoch-Schönlein purpura is more frequent in the West Midlands than previously reported, and Kawasaki disease has a higher incidence than previously indicated in the UK, with the highest incidence in Indian subcontinental Asian children. Other vasculitis is rare in childhood.

Use of antineutrophil cytoplasmic autoantibodies in diagnosing vasculitis in a Chinese patient population.

Antineutrophil cytoplasmic autoantibodies (ANCA) have been used as markers of systemic vasculitides, including microscopic polyarteritis (MPA) and Wegener's granulomatosis. The diagnostic potential of ANCA assays together with antibodies against the neutrophil enzymes myeloperoxidase (MPO) and proteinase 3 for detecting a systemic vasculitis was tested in a Chinese patient population. 672 sera were received for ANCA assay, and ANCA detected by indirect immunofluorescence was positive in 73 sera from 42 patients. Of the 42 patients, 3 had cytoplasmic ANCA, while 39 had a perinuclear pattern. There was no patient with Wegener's granulomatosis. Two cytoplasmic ANCA positive patients suffered from ulcerative colitis. Another cytoplasmic ANCA positive patient was a carrier of human immunodeficiency virus. Of the 39 perinuclear ANCA positive patients, 10 had MPA. Eight of them were tested for anti-MPO antibody, and all were positive. Other immune disorders that were perinuclear ANCA positive included: 13 patients with systemic lupus erythematosus, 3 with mixed connective tissue disease, 1 with Goodpasture's syndrome, 2 with inflammatory bowel disease, and 2 patients with IgA nephropathy. Anti-MPO antibody was not specific for MPA, and 7 out of the 13 patients with systemic lupus erythematosus were anti-MPO antibody positive. Our study suggests that ANCA and anti-MPO antibody are not specific for MPA in a Chinese population. They would alert the clinician of the possibility of vasculitis, but a clinicopathological correlation is essential in making the diagnosis.

Cell-matrix interactions in Schistosomal portal fibrosis: a dynamic event

In recent years, one of the most significant progress in the understanding of liver diseases was the demonstration that liver fibrosis is a dynamic process resulting from a balance between synthesis and degradation of several matrix components, collagen in particular. Thus, fibrosis has been found to be a very early event during liver diseases, be it of toxic, viral or parasitic origin, and to be spontaneously reversible, either partially or totally. In liver fibrosis cell matrix interactions are dependent on the existence of the many factors (sometimes acting in combination) which produce the same events at the cellular and molecular levels. These events are: (i) the recruitment of fiber-producing cells, (ii) their proliferation, (iii) the secretion of matrix constituents of the extracellular matrix, and (iv) the remodeling and degradation of the newly formed matrix. All these events represent, at least in principle, a target for a therapeutic intervention aimed at influencing the experimentally induced hepatic fibrosis. In this context, hepatosplenic schistosomiasis is of particular interest, being an immune cell-mediated granulomatous disease and a model of liver fibrosis allowing extensive studies in human and animals as well as providing original in vitro models.