Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wegener's granulomatosis (WG) is a systemic inflammatory disease with vasculitis as the key feature. Abnormal expression of tumour necrosis factor alpha (TNFalpha) is considered of prime pathogenic importance in several inflammatory diseases. The effects of TNFa are mediated by TNF receptors (TNF-R), and these receptors are often found in soluble forms (sTNF-R), which can modulate TNFalpha actions. To evaluate the clinical importance of the TNF family of cytokines, the serum levels of TNFalpha, TNFbeta, now termed lymphotoxin (LTalpha), and sTNF-R1 and sTNF-R2 were measured by ELISA in 8 patients with WG during active disease and during immunosuppressive treatment, and in 11 healthy controls in parallel. Serum concentrations of TNFalpha were undetectable in all except two controls (18%) and three patients with WG (37%). After 7 days of therapy, six of the WG patients had measurable TNFalpha levels. Examination of the relative amounts of TNFalpha and sTNF-R indicated that TNFalpha was mostly bound to its soluble receptors. In WG, the serum levels of sTNF-R1 and sTNF-R2 were dramatically increased (p<0.01), with little or no variation during treatment. While the IL-1beta levels did not deviate significantly from controls, the IL-1ra levels were significantly elevated in the WG patients throughout the study period (p<0.01).
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PMID:Tumour necrosis factor-alpha (TNF), lymphotoxin and TNF receptor levels in serum from patients with Wegener's granulomatosis. 1190 58

Pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) is unresolved. Dysregulation of programmed cell death is discussed as a pathogenetic factor. We have previously shown that increased in vitro apoptosis of cultured peripheral blood mononuclear cells (PBMC) is nonspecific for SLE. Importantly, however, in recent experiments with SLE PBMC from patients with infections and fever in vitro apoptosis was strongly accelerated. We therefore hypothesized that regulation of apoptosis might be disturbed in activated SLE lymphocytes. Thus, we generated phytohemagglutinine (PHA)/IL-2 stimulated lymphoblasts in vitro. These lymphoblasts readily undergo apoptosis after culture in cytokine-free medium, and can be rescued by addition of gammac-chain cytokines IL-2, -4, -7, or -15. In lymphoblasts from 60 SLE patients tested in comparison to lymphoblasts from normal donors cultured in parallel, we found significant hyporesponsiveness to gammac-chain cytokines in SLE cells. Minor differences were also seen in lymphoblasts from patients with other systemic autoimmunopathies (mixed connective tissue disease, vasculitis, n=49)and in lymphoblasts from patients with other autoimmune diseases (mainly rheumatoid or reactive arthritis, myositis, n=44). In patients with high erythrocyte sedimentation rate (> 25 mm/h), TNF-alpha (> 6.5 pg/ml) or IL-12 (> 4.7 pg/ml) serum levels or detectable IFN-gamma concentrations hyporesponsiveness to gammac-chain cytokines was even more pronounced in SLE lymphoblasts, but not in lymphoblasts from the other groups. Moreover, increased apoptosis was seen in lymphoblasts from SLE patients with decreased complement (C)4 or elevated dsDNA antibody levels. In conclusion, these data suggest that in SLE patients with increased inflammatory activity and/or Th1 dominance signaling through gammac-chain cytokine receptors is deteriorated, leading to facilitated apoptosis of activated lymphocytes and enlarged onflow of apoptotic material.
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PMID:Hyporesponsiveness to gammac-chain cytokines in activated lymphocytes from patients with systemic lupus erythematosus leads to accelerated apoptosis. 1198 12

Juvenile dermatomyositis (JDM) is a multisystem disease characterized by acute and chronic lymphocytic inflammation of the skeletal muscle and skin. The disease is marked early in its course by the presence of a vasculopathy or vasculitis, and later by the development of calcinosis. Research has focused on the epidemiology, etiology, and pathogenesis of the disease with, until more recently, limited therapeutic interventions. This article highlights treatment regimens, both traditional and more recent interventions. Traditional treatment for JDM includes high dose corticosteroid treatment with additional agents used in resistant disease or children with unwarranted adverse effects. Traditional therapy begins with daily oral corticosteroids, with intravenous corticosteroids utilized in severe disease; however, recent data suggests that short-term use of intravenous corticosteroids will allow a short-term improvement in strength, with no long-term change in outcome. More recent investigations suggest that early intervention with additional immunomodulatory agents will allow for a faster recovery, with less medication and disease sequelae. Use of methotrexate as an agent early in the disease course is becoming common place. Methotrexate, in conjunction with oral corticosteroids, allows a rapid improvement in symptoms, and allows for a more rapid reduction in corticosteroid dose. Methotrexate is considered as a steroid sparing agent, whether oral or intravenous corticosteroids are used. Additional immunomodulatory agents include the use of cyclosporine with or without methotrexate. Intravenous immunoglobulin has been reported to have benefit in resistant disease. There are exciting new agents which have great potential in treating JDM. Many of these agents are termed biologics and are being tested in adult myositis and juvenile arthritis. These include tumor necrosis factor (TNF)-alpha inhibitors, such as a chimeric monoclonal antibody to TNF-alpha, and a recombinant soluble human TNF receptor (p75)-Fc fusion protein. Many other new biological agents are also being tested in myositis.
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PMID:Juvenile dermatomyositis: recognition and treatment. 1199 36

The cause or mechanism of the female predisposition in systemic lupus erythematosus and progressive systemic sclerosis is largely unknown. Accumulating evidence shows that dysfunction or activation of endothelial cells plays an important role in these conditions. In this study, we investigated the influence of various steroid hormones on the IL-1beta (50 U/mL)/TNF-alpha (50 U/mL) stimulated human dermal microvascular endothelial cell line (HMEC-1) and human umbilical vein endothelial cells (HUVEC). Dexamethasone showed significant inhibition of cytokine-induced ICAM-1 expression in HMEC-1, and E-selectin, VCAM-1 and ICAM-1 expressions in HUVEC. Androgens, especially dihydrotestosterone had a small, but statistically significant suppressive effect in HMEC-1 only. Estrogen exhibited no regulatory function in either cell line. No obvious expression of estrogen and androgen receptors could be demonstrated in either cell by immunostaining. Our study provided some pharmacological evidence that the superior anti-inflammatory effect of glucocorticoids on vasculitis was partly due to their inhibition of the CAM expression in endothelial cells. More studies are needed to determine if androgens could have a protective effect in vasculitis or vasculopathy associated with connective tissue diseases.
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PMID:Effects of dexamethasone and sex hormones on cytokine-induced cellular adhesion molecule expression in human endothelial cells. 1237 Jan 31

Viral infection of the vascular wall cellular elements is involved in development of several pathophysiological events, including vasculitis, transplant rejection, and atherosclerosis. Previously, we have shown that cultured human vascular endothelial cells (ECs) may be effectively infected with herpes simplex type I virus (HSV-1), and this cultural model could be a useful tool for the explanation of many aspects of viral disease. In this study, we investigated the effects of conditioned media (CM) of peripheral blood mononuclear cells (PBMCs) on HSV-1 reproduction and cell adhesion molecule expression in cultured ECs. PBMC-CM induced the delay of virus reproduction or inhibition of virus reproduction. Effects of CM correlated with multiplicity of infection used for EC, time of PBMC contact with infected and glutaraldehyde-fixed endothelium, and the level of IFNs and cytokine production. Passages of and CM-treated and infected cells without signs of virus reproduction were, sometimes, followed by virus reactivation. However, at a low level of infection of CM-treated ECs the virus reactivation was not observed even after 2-3 cell passages. Neutralizing antibodies against IFN-alpha, IFN-gamma, and TNF-alpha, used separately or together, significantly abrogated the delaying and/or inhibiting action of CM. Additionally, PBMC-CM significantly increased the expression of ICAM-1 and VCAM-1 on cultured ECs. The strongest cell activation was induced by CM obtained from PBMCs co-incubated with virus-infected endothelium. Obtained results suggest that primed leukocytes produce soluble factors with either anti-viral or pro-inflammatory activity, and the effect of PBMC-CM may have a bi-directional action. On the one hand, due to production of interferons and several cytokines CM sets up HSV-1 latency or virus elimination from cultured cells. On the other, the same cytokines act on infected and/or neighboring ECs and initiate the cascade of inflammatory reactions in the vascular wall.
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PMID:Herpes simplex type I virus infected human vascular endothelial cells induce the production of anti-viral and proinflammatory factors by peripheral blood leukocytes in vitro. 1268 53

Infliximab is an antibody to tumor necrosis factor (TNF) that is used in the treatment of Crohn disease and rheumatoid arthritis. This medication neutralizes TNF-alpha by binding to TNF receptors and inhibiting further induction of proinflammatory cytokines. We describe a patient with Crohn disease who developed hypersensitivity vasculitis with biopsy-proven leukocytoclastic vasculitis 9 days after her initial dose of infliximab. To our knowledge, this is the first reported case of infliximab-induced hypersensitivity vasculitis with leukocytoclastic vasculitis that occurred after the first dose of drug. It is important to note that hypersensitivity vasculitis can occur secondary to administration of this drug, even after the initial exposure.
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PMID:Hypersensitivity vasculitis with leukocytoclastic vasculitis secondary to infliximab. 1270 83

Various adverse cutaneous reactions to anti-TNF-alpha monoclonal antibody have been reported. In clinical studies with infliximab (Remicade) adverse drug reactions were most frequently reported in the respiratory system and in the skin and appendages. We describe here 6 patients receiving anti- TNF-alpha therapy (infliximab) for Crohn's disease or rheumatoid arthritis who consulted our out-patient department for adverse cutaneous reactions between November 1999 and February 2002. The following diagnoses were made: leukocytoclastic vasculitis, lichenoid drug reaction, perniosis-like eruption (2 patients), superficial granuloma annulare and acute folliculitis.
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PMID:Adverse skin reactions to anti-TNF-alpha monoclonal antibody therapy. 1277 94

As experience with anti-tumor necrosis factor (TNF-alpha) therapy increases, there has been the expected emergence of reports on uncommon side effects. Large clinical trials identified the development of autoantibodies and postmarketing surveillance has identified problems including tuberculosis. There have been several case reports of drug-induced systemic lupus erythematosus. We describe eight patients with rheumatoid arthritis treated with anti-TNF therapies who developed presumed vasculitis, with different pathophysiologic causes. We discuss the literature and potential causal mechanisms, including disease activity, the role of autoantibodies, and shifts in T cell responses.
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PMID:Anti-tumor necrosis factor-alpha therapy-induced vasculitis: case series. 1522 72

Feline infectious peritonitis virus (FIPV) is a coronavirus that causes sporadic fatal disease in cats characterized by vasculitis, granulomatous inflammation and effusive pleuritis/peritonitis. Histologic changes in lymphoid tissues include lymphoid hyperplasia, lymphoid depletion, histiocytosis, and granuloma formation. Although viremia occurs, histologic lesions are not found uniformly throughout lymphoid tissues. We used experimental infection of cats with a highly pathogenic FIPV isolate, UCD8, to study histologic lesions, virus replication, and cytokine expression in multiple lymphoid tissues during the effusive phase of disease. Viral RNA was found in 76% of central tissues (mediastinal lymph node, spleen, mesenteric lymph node) examined, as compared to 27% of peripheral tissues (popliteal lymph node, cervical lymph node, femoral bone marrow). All tissues positive for virus replication also demonstrated lymphoid depletion. Generally, affected tissues had lower levels of IL-4 and IL-12-p40 mRNA and higher levels of IL-10 mRNA. Although no differences in IFN-gamma or TNF-alpha mRNA were measured, TNF-alpha protein expression was greater in affected tissues and demonstrated a shift in the source of TNF-alpha from macrophages to lymphocytes. Together, these results colocalize FIPV replication, lymphocyte depletion in tissues, and alterations in cytokine transcription and translation. A possible role for TNF-alpha in the previously described FIPV-induced lymphocyte apoptosis is also suggested.
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PMID:In vivo cytokine response to experimental feline infectious peritonitis virus infection. 1463 34

Tumor necrosis factor (TNF)-alpha plays a major role in the pathogenesis of Kawasaki disease (KD), a systemic vasculitis primarily affecting young children. We performed this study to examine the serum levels of TNF-alpha and to investigate a possible relation to promoter polymorphism at positions -238 and -308 in KD patients in Korea. We obtained 48 paired serum samples from 24 patients in the acute and subacute stages of KD, and control sera from 12 age-matched children who were having routine blood samples taken before elective surgical procedures. Our studies showed a significant increase in serum levels of TNF-alpha measured in the acute stage of KD (24.1 +/- 9.4 pg/mL) compared to those in the subacute stage (11.8 +/- 5.8 pg/mL; p < 0.01) and normal controls (10.4 +/- 4.9 pg/mL; p < 0.01). Previous studies report that the presence of the A allele at positions -308 and -238 may be associated with higher TNF-alpha levels. However, our results showed that the frequency of the A allele at position -308 in the KD patients was the same as the controls (2 out of 24, 8.3% vs. 8.3%, odds ratio (OR)= 1.00), while the frequency of the A allele at position -238 in the KD patients was lower than the controls (0/24, 0% vs. 8.3%, OR=0.00); this difference though was not statistically significant. We concluded that although TNF-alpha levels were significantly elevated in the acute stage of KD, there was no significant difference in the frequency of the A allele at positions -238 and -308 between the KD and control groups in Korean patients.
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PMID:Tumor necrosis factor-alpha levels and promoter polymorphism in patients with Kawasaki disease in Korea. 1470 11


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