scholarly journals Cytokines and MMP-9 Levels in Rheumatoid Arthritis and Osteoarthritis Patients with Persistent Parvovirus B19, HHV-6 and HHV-7 Infection

Author(s):  
Anda Kadiša ◽  
Zaiga Nora-Krūkle ◽  
Simons Švirskis ◽  
Pēteris Studers ◽  
Irute Girkontaite ◽  
...  

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes erosive changes and ankylosis of joints and may cause internal injuries. Osteoarthritis (OA) is a degenerative process of the articular cartilage. However, inflammatory mediators may play a pivotal role in the initiation and perpetuation of the OA process. It is necessary to continue to study possible factors that may promote the development of the disease. The goal of this study was to evaluate the frequency and activity stage of parvovirus B19 (B19V) and persistent human herpes virus (HHV)-6 and HHV-7 infection in RA and OA patients, and healthy persons, in relation to cytokine levels and presence or absence of viral infections. RA patients with active B19V infection had the highest levels of tumour necrosis factor alpha (TNF-α), which may contribute to the development of RA. In the case of OA, the TNF-α level was higher in patients with active persistent B19V infection, suggesting that B19V reactivation affects also OA. Interleukin (IL)-6, IL-10 and metalloproteinase (MMP)-9 levels were higher in RA patients with latent HHV-6/-7 infection in comparison with active HHV-6/-7 infection, whereas in OA patients levels of all studied cytokines were very variable, ranging from low to high but without significant differences. This suggests that also latent HHV-6 and -7 viral infections can promote development of RA.

2002 ◽  
Vol 76 (11) ◽  
pp. 5395-5403 ◽  
Author(s):  
Yi Fu ◽  
Keiko Kumura Ishii ◽  
Yasuhiko Munakata ◽  
Takako Saitoh ◽  
Mitsuo Kaku ◽  
...  

ABSTRACT Human parvovirus B19 frequently causes acute and chronic arthritis in adults. The molecular mechanism of B19 arthritis, however, remains poorly understood. We previously showed that the transmission of B19 from rheumatoid synoviocytes to monocytic cells is associated with enhanced secretion of tumor necrosis factor alpha (TNF-α), which triggers inflammation, and interleukin-6. To determine the role of B19 in the production of TNF-α, we focused on the function of its nonstructural protein, NS1, and established monocytic U937 lines transduced with the NS1 gene under the control of an inducible promoter. Production of TNF-α mRNA and protein was elevated in a manner associated with NS1 expression. Reporter assays revealed that AP-1 and AP-2 motifs on the TNF-α promoter were responsible for NS1-mediated up-regulation. Electrophoretic mobility shift assay showed specific binding of nuclear proteins from NS1 gene-transduced cells with the AP-1 or AP-2 probe. Antibodies against transcription factors AP-1 and AP-2 and anti-NS1 antibody inhibited the binding of nuclear proteins to the corresponding probes. These data indicate that NS1 up-regulates TNF-α transcription via activation of AP-1 and AP-2 in monocytic cells. The molecular mechanisms of NS1-mediated TNF-α expression would explain the pathogenesis of B19-associated inflammation.


2001 ◽  
Vol 69 (11) ◽  
pp. 6912-6922 ◽  
Author(s):  
Annette Kolb-Mäurer ◽  
Alexandra Unkmeir ◽  
Ulrike Kämmerer ◽  
Claudia Hübner ◽  
Thomas Leimbach ◽  
...  

ABSTRACT Infection with Neisseria meningitidis serogroup B is responsible for fatal septicemia and meningococcal meningitis. The severity of disease directly correlates with the production of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-8. However, the source of these cytokines has not been clearly defined yet. Since bacterial infection involves the activation of dendritic cells (DCs), we analyzed the interaction of N. meningitidis with monocyte-derived DCs. Using N. meningitidis serogroup B wild-type and unencapsulated bacteria, we found that capsule expression significantly impaired neisserial adherence to DCs. In addition, phagocytic killing of the bacteria in the phagosome is reduced by at least 10- to 100-fold. However, all strains induced strong secretion of proinflammatory cytokines TNF-α, IL-6, and IL-8 by DCs (at least 1,000-fold at 20 h postinfection [p.i.]), with significantly increased cytokine levels being measurable by as early as 6 h p.i. Levels of IL-1β, in contrast, were increased only 200- to 400-fold at 20 h p.i. with barely measurable induction at 6 h p.i. Moreover, comparable amounts of cytokines were induced by bacterium-free supernatants of Neisseria cultures containing neisserial lipooligosaccharide as the main factor. Our data suggest that activated DCs may be a significant source of high levels of proinflammatory cytokines in neisserial infection and thereby may contribute to the pathology of meningococcal disease.


Author(s):  
B B Fishman ◽  
M A Toneeva ◽  
V E Kulikov ◽  
V A Kornilova ◽  
E R Antonova

The research objectives are to determine serum interleukins (IL-2, IL-6) and tumor necrosis factor alpha (TNF - α) and evaluate their interrelation in liver cirrhosis (class A, B, C according to Chad - Pugh). 117 patients were examined and their cytokines levels were determined using enzyme-linked immunosorbent assay.Elevation of cytokine levels IL-2, I-6 and TNF-α within reference values was found in liver cirrhosis cases, expect for level IL-6 in liver cirrhosis cases of class C. In these cases IL-6 level exceeds reference values and is within the limit of 9,94 - 25,21 pg / ml with average concentration of 14,89±4,96 pg / ml. Correlation is found between TNF- α and IL-6 (r = - 0,499) in liver cirrhosis of class A and correlation between TNF- α and IL-2 (r = 0,421) is found in liver cirrhosis of class B.


2020 ◽  
Vol 33 (04) ◽  
pp. 243-251
Author(s):  
Bahar Gerivani ◽  
Hamid Staji ◽  
Maryam Rassouli ◽  
Nooshin Ghazaleh ◽  
Abbas Javaheri Vayeghan

Abstract Objective Erythromycin (Ery) and leech saliva (LS) can inhibit Staphylococcus aureus growth in in vitro conditions. This study aimed to evaluate the activities and synergy between Ery and LS on chronic osteomyelitis in male Wistar rat's tibia induced by methicillin-resistant S. aureus (MRSA). Materials and Methods Four weeks after osteomyelitis induction, rats were divided into four groups including no treatment (control), Ery monotherapy (orally), LS monotherapy, or Ery + LS twice daily for 2 weeks. Staphylococcus aureus growth, pathological signs and inflammatory cytokine tumour necrosis factor-alpha (TNF-α) levels were assessed. Results Rats tolerated all therapeutic strategies well during the experiment. The Ery treatment alone significantly decreased bacterial growth, pathological signs and TNF-α levels. Leech saliva alone reduced TNF-α level significantly, but did not produce a significant reduction in bacterial growth and pathological signs. Ery + LS treatment significantly decreased bacterial growth, considerably alleviated bone pathological signs and decreased TNF-α levels compared with other groups. Statistical analysis suggested that there was a stronger efficiency and synergistic action of Ery and LS when combined against MRSA-induced osteomyelitis in rats. Clinical Significance The present study suggests that LS may have clinical utility to treat MRSA-induced osteomyelitis when combined with Ery or other therapeutics.


2012 ◽  
Vol 19 (5) ◽  
pp. 699-703 ◽  
Author(s):  
Eric Assier ◽  
Luca Semerano ◽  
Emilie Duvallet ◽  
Laure Delavallée ◽  
Emilie Bernier ◽  
...  

ABSTRACTTumor necrosis factor alpha (TNF-α) blockade is an effective treatment for patients with TNF-α-dependent chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. TNF-α kinoid, a heterocomplex of human TNF-α and keyhole limpet hemocyanin (KLH) (TNF-K), is an active immunotherapy targeting TNF-α. Since the TNF-K approach is an active immunization, and patients receiving this therapy also receive immunosuppressant treatment, we evaluated the effect of some immunosuppressive drugs on the generation of anti-TNF-α antibodies produced during TNF-K treatment. BALB/c mice were injected intramuscularly with TNF-K in ISA 51 adjuvant. Mice were also injected intraperitoneally with one of the following: phosphate-buffered saline, cyclophosphamide, methylprednisolone, or methotrexate. Anti-TNF-α and anti-KLH antibody levels were assessed by enzyme-linked immunosorbent assay and the anti-TNF-α neutralizing capacity of sera by L929 bioassay. Our results showed that current treatments used in rheumatoid arthritis, such as methylprednisolone and methotrexate, do not significantly alter anti-TNF-α antibody production after TNF-K immunization. In contrast, the administration of cyclophosphamide (200 mg/kg) after immunization significantly reduced anti-TNF-α antibody titers and their neutralizing capacity.


2015 ◽  
Vol 9 (3) ◽  
pp. 288
Author(s):  
Rostika Flora ◽  
Mukni Mukni ◽  
Bina Melvia Girsang ◽  
Sigit Purwanto

Ibu hamil yang berada di daerah endemis malaria sangat rentan terhadap infeksi malaria selama kehamilan. Gejala malaria pada kelompok ini sering asimptomatik atau bahkan tidak terdeteksi sama sekali karena adanya efek imunitas protektif melalui infeksi yang berulang. Adanya peningkatan kadar tumor necrosis factor-alpha (TNF-α) dapat dijadikan indikator terjadinya infeksi malaria. TNF-α berperan penting dalam respons imun pada malaria akut yang menghambat terjadinya eritropoesis. Penelitian ini bertujuan untuk mengetahui hubungan antara kadar TNF-α dengan kejadian anemia pada ibu hamil didaerah endemik malaria vivax. Penelitian ini menggunakan desain potong lintang, dilakukan pada bulan Januari - Februari 2014 di lima wilayah kerja puskesmas Kota Bengkulu. Sampel penelitian adalah ibu hamil di daerah endemis malaria vivax yang diambil secara accidental sampling. Dilakukan pengambilan darah untuk pemeriksaan mikroskopis malaria, kadar TNF-α dan kadar hemoglobin (Hb). Hasil penelitian menunjukkan seluruh ibu hamil memiliki riwayat pernah terinfeksi malaria vivax, walaupun hasil pemeriksaan slide negatif. Terjadi peningkatan kadar TNF- α dengan rerata 6,90 ± 2,48 pg/mL dan penurunan kadar Hb dengan rerata 9,75 ± 0,88 g%. Uji korelasi Spearman didapatkan korelasi negatif yang kuat (r = -0,734) dan bermakna (nilai p < 0,05) antara Kadar TNF-α dengan kadar Hb. Terdapat hubungan yang bermakna antara kadar TNF-α dengan kejadian anemia.Tumor Necrosis Factor-α as Predictor of Anemia Occurrence among Pregnant Mothers in Malaria-Endemic AreasPregnant mothers living in malaria - endemic area are very susceptible to malaria infection during pregnancy. Malaria symptoms in this group are often asymptomatic or even not detected at all due to protective immunity effect through repeated infections. Any elevation of tumor necrosis factor-alpha (TNF-α) level can be used as indicator of malaria infection. TNF-α takes an important role in immune response on acute malaria that hinders occurence eritropoesis process. This study aimed to find out relations between TNF-α level and anemia occurrence among pregnant women living in malaria vivax - endemic areas. The study used cross-sectional design conducted on January to February 2014 in five working areas in Bengkulu city. Sample of study was pregnant mothers in malaria vivax - endemic areas which was taken through accidental sampling. Blood was taken for malaria-microscopic examination, TNF-α and haemoglobine (Hb) level. The results showed that all of pregnant mothers have malaria vivax - infected record, although slide examination showed negative result. Any TNF-α level elevation with average 6.90 ± 2.48 pg/mL and decrease of Hb level with average 9.75 ± 0.88 g%. Spearman correlation test showed strong negative correlation (r = -0.734) and significant (p value < 0.05) between TNF-α level and Hb level. There was significant relation between TNF-α level and anemia occurrence.


2017 ◽  
Vol 3 (2) ◽  
pp. 74
Author(s):  
Muhammad Ali Apriansyah ◽  
Rudi Putranto ◽  
Eddy Mart Salim ◽  
Hamzah Shatri

Pendahuluan. Prevalensi depresi hamper mencapai 50% pada pasien yang berobat di pelayanan tertier klinik asma. Tumor Necrosis Factor-Alpha (TNF-α) telah diketahui sebagai sitokin pro-inflamasi yang berperan penting dalam mekanisme patogenesis sejumlah penyakit inflamasi kronik, termasuk asma bronkial dan depresi. Belum ada data penelitian mengenai hal tersebut di Indonesia.Metode. Penelitian ini merupakan studi cross sectional yang dilakukan pada 40 pasien asma bronkial tidak terkontrol di alergi imunologi klinik unit rawat jalan Rumah Sakit Umum Pusat (RSUP) Moh Hoesin Palembang selama kurun waktu mulai bulan Juni 2014 sampai dengan Agustus 2014. Asma bronkial tidak terkontrol dinilai dengan menggunakan kuesioner Asthma Control Test (ACT), sedangkan gejala depresi dinilai dengan kuisioner Beck Depression Inventory (BDI). Konfirmasi diagnosis depresi dilakukan dengan kriteria dari Diagnostic and Statistical Manual for Psychiatry-IV Text Revision (DSMIV TR)/ International Code Diagnose 10 (ICD-10). Sementara itu, kadar TNF-α serum diukur dengan metode quantitative enzyme-linked immunosorbent assay (ELISA).Hasil. Nilai median tingkat depresi dan TNF-α serum pada penelitian ini adalah 16 (10 – 45) dan 4,09 (1,29 – 19,57) pg/mL.Tidak didapatkan korelasi yang bermakna secara statistik antara tingkat depresi dan kadar TNF-α (r = -0,265, p = 0,098).Simpulan. Tidak didapatkan korelasi yang bermakna antara tingkat depresi dengan kadar TNF-α pada penderita asma bronkial tidak terkontrol.Kata Kunci: asma bronkial tidak terkontrol, kadar TNF-α, Tingkat depresi The Correlation of Depression Level with Tumor Necrosis Factor-Alpha (TNF-α) Concentration in Uncontrolled Bronchial Asthma PatientsIntroduction. Depression occurs at high rates in people with chronic diseases, including bronchial asthma, with the prevalence of depression approaches 50% in tertiary care asthma clinic. Tumor necrosis factor alpha (TNF-α) is known to play a critical role in the pathogenic mechanism of a number of chronic inflammatory disease, including bronchial asthma and depression. There has not been any research data on the subject in Indonesia. The objective of this study was to investigate the correlation between depressive level and TNF-α level in uncontrolled bronchial asthma. Methods. This was a cross sectional study conducted in 40 patients with uncontrolled bronchial asthma at the allergy immunology clinic outpatient of Dr Moh Hoesin Hospital Palembang, during June 2014 until August 2014. Uncontrolled bronchial asthma was assessed using the Asthma Control Test (ACT) questionnaire, whereas depressive symptoms were assessed by Beck Depression Inventory (BDI) questionnaire, and diagnosis was confirmed by the criteria of the Diagnostic and Statistical Manual for Psychiatry-IV Text Revision (DSM-IV TR) / International Code Diagnose 10 (ICD-10). Serum levels of TNF-α was measured by the method of quantitative enzyme-linked immunosorbent assay (ELISA). Results. The median value of the level of depression and serum TNF- α in this study were 16 (10 - 45) and 4.09 (1.29 - 19.57) pg/mL. There was no significant correlation between depressive level and TNF-α level ( r = -0.265 , p = 0.098 ). Conclusions. There was no significant correlation between depressive level and TNF-α level in uncontrolled bronchial asthma Keywords: depressive level, TNF-α level, uncontrolled asthma bronchial


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