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Meier, Remy
"The pathogenesis of inflammatory bowel disease (IBD) is not yet fully understood A genetic predisposition, some environmental factors and microbial flora of the grit are the key factors. The presence of bacteria in the intestinal lumen is a prerequisite for the development of IBD. In animal models, mice incapable of expressing IL, or IL invariably develop a colitis- or Crohn-like inflammation. No inflammation occurs if they grow up in a pathogen free environment or if they are fed with Lactobacillus sp when exposed to environmental bacteria. Thus, the absence of liminal bacteria or a different make-up there of prevents the development of inflammatory bowel disease in this model. Patients with IBD have been found to have a decreased stool excretion Lactobacillus andlor Bifidobacteria.
Furthermore, an increased number of bacteria adherents to the mucosa and within the epithelium has been demonstrated in quantitative studies. It appears that these bacteria trigger a strong abnormal mucosal immunological response, leading to intestinal epithelial cell injury mediated by activated T-cells, mononuclear cells and macrophages. If this response can not be down regulated by regulatory T-cells, mononuclear inflammatory cytokines are activated by stimulation of the intracellular transcription factor NF-kB. Recently it was shown that bacterial lipopolysaccharides can activate NF-kB by binding to two specific receptors on the cell membrane (Toll-like receptors [TLR's]) or intracellular receptors (NOD's).
New insights of the role of bacteria in IBD became available by identifying susceptibility genes for IBD. Several IBD susceptibility loci were recently identified. The IBD-l locus on chromosome 16 shows positive evidence for linkage in Crohn's disease and IBD-2 locus on chromosome l2 for ulcerative colitis. The evidence for' an association with Crohn's disease at the IBD-I locus have been shown to be attributed to mutations in the CARDI5/NOD2 gene. This gene is exressed in peripheral blood monocytes and in intestinal epithelial cells and serves as a key factor of innate mucosal response to luminal bacteria as an antibacterial factor.
The intact intercellular NOD2 protein binds LPS and activates NF-kB. This activation of the NF-kB signalling pathway in response to bacterial components plays a protective role in the mucosal epithelial cells for the host against inviting pathogens and an increased apoptosis of infected cells. There is evidence, that the defective NOD2 protein variants increase the susceptibility to pathogen invasion and a decrease in cellular apoptosis.
NF-kB plays a dual role in IBD. On the mucosal epithelial cells, bacterial components bind on NOD2 proteins and protect bacterial invasion. If this barrier mechanism is not intact, the bacterial invasion stimulates via TLR- and NOD2 receptors in immune-active cells (macrophages, T-cells and monocytes) NF-kB and triggers an aberrant inflammatory response leading to tissue damage. These new insights in the pathogenesis in IBD have led to new treatment possibilities including pre- and probiotics.
These therapies are aimed at directly modulating the host immune system to suppress intestinal inflammation. This has prompted considerable interest in manipulating the enteric microenvironment as a novel therapeutic strategy Several clinical studies showed promising results rising pre- and probiotics in patients with ulcerative colitis, pouchitis and Crohn's disease. The introduction of genetically engineered probiotic organism to produce and deliver anti-inflammatory cytokines or other biological relevant molecules to the mucosa offers further new potential for the treatment of IBD."
Jakarta: The Indonesian Journal of Gastroenterology Hepatology and Digestive Endoscopy, 2003
IJGH-4-2-Agt2003-50
Artikel Jurnal  Universitas Indonesia Library
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Mine Erguven, editor
"This book summarizes the extensive up-to-date literature overeview with the lastest work of experts about midkine in a detailed format that conveys its role as both a pathologic factor and therapeutic agent."
Dordrecht: [, Springer], 2012
e20417490
eBooks  Universitas Indonesia Library
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Arto Y. Soeroto
"Background: Toll-like receptor is a pattern recognition receptor (PRR) that recognize pathogen-associated molecular pattern (PAMP) in a microorganism. Macrophages recognize the presence of mycobacteria through Toll-Like Receptor 2 (TLR2) and signaling further lead to the production of cytokines, both proinflammatory TNF-α, IL-1β, IL-6, IL-12, IL-15, IL-18 and IFN-γ, as well as anti-inflammatory IL4, IL-10 and TGF-β. TLR2 gene polymorphism is strongly determined by ethnicity and geography. Therefore it is necessary to uncovered the existence and association between Arg753Gln and Arg677Trp TLR2 gene polymorphism with TB susceptibility and its underlying mechanisms in Indonesian population in Bandung West Java. Methods: analytical observational study with cross-sectional design was conducted in Hasan Sadikin General Hospital Bandung from April 2011 to May 2012. Study population consisted of active pulmonary TB patient with positive AFB smear and Latent TB to ascertain previous MTb exposure. Polymorphism of gen Arg753Gln and Arg677Trp gene was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Plasma levels of IFN-γ, TNF-α, IL-10 and IL-12 were also compared between active and latent TB group. Results: heterozygote Arg753Gln TLR2 gene polymorphism was found in 9 of 86 pulmonary TB subjects (10.5%) but none in the latent TB group. The Arg677Trp polymorphism was not found in both groups. The odds ratio for Arg753Gln existence was 28.07 (p=0.022). No differences in the levels of IFN-γ, TNF-α, IL-10 and IL-12 between active pulmonary TB and latent TB subjects with and without Arg753Gln TLR2 gene polymorphism. Conlusion: Arg753Gln polymorphism of TLR2 gene is a risk factor for active pulmonary TB while Arg677Trp polymorphism is not. The Increased risk is not mediated by the difference in IFN-γ, TNF-α, IL-10 and IL-12 serum levels."
Jakarta: Interna Publishing, 2018
610 IJIM 50:1 (2018)
Artikel Jurnal  Universitas Indonesia Library
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Maya Ulfah
"Latar Belakang: Coronavirus disease 2019 (COVID-19) adalah penyakit infeksi saluran pernapasan yang pertama kali ditemukan di Wuhan. Sejak ditetapkan sebagai pandemi oleh WHO hingga 3 Juli 2021 terdapat sebanyak 183.098.615 kasus terkonfirmasi positif COVID-19 dengan jumlah kematian sebesar 3.964.145 kasus di seluruh dunia. Secara etiologi COVID-19 disebabkan oleh varian coronavirus baru yang dikenal sebagai SARS-CoV-2. Individu yang terinfeksi SARS-CoV-2 sebagian besar mengalami gejala ringan atau asimtomatik. Namun, pada sebagian orang dengan usia lanjut dan mengidap penyakit komorbid manifestasi gejala berat lebih sering ditemui. Salah satu faktor yang berkaitan terhadap manifestasi COVID-19 adalah respons imun host. Molekul sitokin merupakan protein yang berperan untuk mengaktifkan mekanisme perlawanan terhadap virus. Pengetahuan tentang profil imunitas yang diperantarai oleh sitokin dari saluran napas atas masih sangat sedikit sekali yang dipelajari. Penentuan biomarker yang dapat dijadikan penanda keparahan juga perlu untuk diketahui.
Metode: Sampel swab NP diperoleh dari pasien terkonfirmasi positif COVID-19. Subjek dibagi menjadi 2 kategori berdasarkan manifestasi COVID-19 gejala ringan dan berat. Kadar sitokin (pg/ml) IL-2, IL-4, IL-10, IL-13, IL-17A, dan GMCSF dianalisis dari sampel swab NP menggunakan Luminex® assay.
Hasil: Faktor demografi seperti usia (p=0,024) dan komorbid (p=0,017) secara signifikan berperan dalam menentukan keparahan gejala pada pasien COVID-19. Kadar (pg/ml) IL-2, IL-4, IL-10, IL-13, IL-17A, dan GMCSF antara kedua kelompok pasien COVID-19 gejala ringan dan berat tidak berbeda signifikan. Namun demikian, terdapat kecenderungan bahwa kadar (pg/ml) IL-2, IL-4, IL-13, dan GMCSF meningkat pada kelompok pasien COVID-19 gejala berat. Sedangkan, kadar (pg/ml) IL-10 dan IL-17A cenderung menurun pada pasien COVID-19 yang bergejala berat. Selain itu, rasio antara IL-2/IL-10 secara signifikan (p=0,004) lebih tinggi pada pasien COVID-19 gejala berat. Sebanyak 65,7% pasien COVID-19 dengan gejala berat memiliki nilai rasio IL-2/IL-10 yang tinggi.
Kesimpulan: Kadar sitokin (pg/ml) IL-2, IL-4, IL-10, IL-13, IL-17A dan kemokin GMCSF (pg/ml) dari sampel swab NP dapat terdeteksi menggunakan Luminex® assay. Rasio kadar sitokin IL-2/IL-10 dapat dijadikan sebagai kandidat biomarker keparahan infeksi COVID-19 di masa mendatang.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory tract infectious disease. Since the outbreak in Wuhan, COVID-19 was declared as a pandemic by WHO. Data from July 3rd, 2021, showed that there have been 183,098,615 confirmed positive cases of COVID-19 with a death toll of 3,964,145 worldwide. Etiologically COVID-19 is caused by the new coronavirus known as SARS-CoV-2. The majority of people infected with SARS-CoV-2 experience mild symptoms or even are asymptomatic. However, for some people with older age and having comorbid diseases, severe manifestations are very common. Host immune response is one of the factors which affect disease severity. Playing a vital role in activating the immune system against viruses, cytokine protein can also contribute to the severity. Currently, very little is known about the profile of cytokine-mediated immunity from the upper respiratory tract. This research is aimed to find a potential candidate of biomarkers to predict severity in the early phase of COVID-19 infections.
Methods: NP swab samples were obtained from patients who were positively confirmed for COVID-19. Subjects were divided into 2 categories based on the manifestation as mild or severe symptoms of COVID-19. Cytokine levels (pg/ml) of IL-2, IL-4, IL-10, IL-13, IL-17A, and GMCSF were analyzed from NP swab samples using Luminex® assay.
Results: Demographic factors such as age (p=0.024) and comorbidities (p=0.017) significantly played a role in determining severity of COVID-19 patients. The levels (pg/ml) of IL-2, IL-4, IL-10, IL-13, IL-17A, and GMCSF between the two groups of patients with mild and severe COVID-19 symptoms were not significantly different. However, there was a tendency that the levels (pg/ml) of IL-2, IL-4, IL-13, and GMCSF to increase in the group of patients with severe COVID-19 symptoms. Meanwhile, levels (pg/ml) of IL-10 and IL-17A tend to decrease in COVID-19 patients with severe symptoms. In addition, the ratio of IL-2/IL-10 was significantly (p=0.004) higher in severe COVID-19 patients. A total of 65.7% of COVID-19 patients with severe symptoms had high values of IL-2/IL-10 ratio.
Conclusion: Cytokine levels (pg/ml) of IL-2, IL-4, IL-10, IL-13, IL-17A, and GMCSF from NP swab samples can be detected using the Luminex® assay. The ratio of IL-2/IL-10 cytokine levels can be used as a biomarker candidate to predict severity for COVID-19 infection in the future.
"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2022
T-pdf
UI - Tesis Membership  Universitas Indonesia Library
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Lubis, Dinda Shezaria Hardy
"Potensi pemanfaatan sel punca mesenkimal dan conditioned medium dalam pengobatan terapi yang tinggi harus diimbangi dengan peningkatan produksi yang memadai. Umumnya menggunakan metode kultur statis (2D), namun produksinya sangat terbatas. Metode kultur dinamis (3D) menggunakan stirred bioreactor merupakan salah satu pilihan yang tepat untuk meningkatkan produksi sel punca dalam skala besar. Selama proses kultur sel, conditioned medium kultur mengandung faktor tumbuh dan sitokin yang disekresikan oleh sel punca mesenkimal. Salah satu sitokin yang disekresikan ialah TGF-β. Sitokin TGF-β berperan penting dalam proliferasi, diferensiasi, dan proses seluler lainnya. Sampai saat ini belum ada penelitian yang menjelaskan tentang pengaruh kultur statis (2D) dan kultur dinamis (3D) terhadap proliferasi sel, total protein conditioned medium dan kadar sekresi sitokin TGF-β pada sel punca mesenkimal asal tali pusat yang dikultur dalam medium alpha-MEM dan disuplementasi 10% thrombocyte concentrated. Tujuan penelitian ini ialah mengetahui pengaruh kultur statis (2D) dan kultur dinamis (3D) terhadap proliferasi sel, kadar total protein conditioned medium, dan sitokin TGF-β pada sel punca mesenkimal asal tali pusat. Penelitian yang dilakukan mencakup proses kultur sel, uji Bradford, Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE), dan uji Enzyme-Linked Immunosorbent Assay (ELISA). Penelitian ini menunjukkan bahwa penggunaan kultur dinamis (3D) dapat memproduksi sel dalam skala besar namun memiliki laju proliferasi yang lebih lama dibandingkan dengan kultur statis (2D). Produksi kadar total protein conditioned medium mengalami fluktuasi, namun secara keseluruhan kultur dinamis (3D) mampu memproduksi dalam skala besar, dan terdapat sekresi sitokin TGF-β oleh sel punca mesenkimal dari kedua metode kultur, namun masih membutuhkan uji lanjutan untuk memastikan bahwa sel pada kultur dinamis (3D) mensekresi sitokin TGF-β lebih banyak

The high potential of mesenchymal and conditioned medium stem cell utilization in therapeutic treatment should be balanced with an adequate increase in production. Generally using static culture method (2D), but production is very limited. Dynamic culture (3D) method using stirred bioreactor is one of the right choices to increase the production of stem cells on a large scale. During the cell culture process, the conditioned culture medium contains growth factors and cytokines secreted by mesenchymal stem cells. One of the cytokines secreted is TGF-β. The TGF-β cytokine plays an important role in proliferation, differentiation, and other cellular processes. Until now there has been no research that explains the effect of static (2D) and dynamic (3D) culture on cell proliferation, total protein conditioned medium and levels of secretion of cytokines TGF-β in mesenchymal stem cells from umbilical cord cultured in alpha-MEM medium and 10% concentrated thrombocyte supplementation. The purpose of this study was to determine the effect of static culture (2D) and dynamic culture (3D) on cell proliferation, levels of total protein in conditioned medium, and cytokine TGF-β in mesenchymal stem cells from the umbilical cord. The research conducted included cell culture process, Bradford test, Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE), and Enzyme-Linked Immunosorbent Assay (ELISA) test. This study shows that the use of dynamic culture (3D) can produce cells on a large scale but has a longer proliferation rate than static culture (2D). The total protein content of the conditioned medium fluctuates, but overall dynamic (3D) culture is capable of large-scale production, and there is secretion of the cytokine TGF-β by mesenchymal stem cells from both culture methods, however, further tests are still needed to confirm that the cells in culture dynamic (3D) secretes more of the cytokine TGF-β."
Depok: Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Indonesia, 2021
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UI - Skripsi Membership  Universitas Indonesia Library
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Diana Sunardi
"ABSTRAK
Pasien kanker umumnya mengalami penurunan berat badan terkait kaheksia. Patofisiologi kaheksia kanker multifaktorial, termasuk efek sitokin pro inflamasi dan inflamasi sistemik. Profil asam amino plasma pada pasien kanker mengalami perubahan. Deplesi protein dapat terjadi akibat asupan yang menurun atau efek langsung dari tumor. Penelitian ini bertujuan untuk mengetahui profil dan hubungan antara asam amino serum, status nutrisi dan sitokin-sitokin pro-anti inflamasi, serta sel T helper 17 pada pasien kaheksia kanker paru. Penelitian potong lintang dengan consecutive sampling pada pasien kanker paru dengan kaheksia ini mengambil subjek berusia lebih dari 18 tahun dan belum diterapi atau sudah selesai terapi lebih dari 2 bulan di Rumah Sakit Kanker Dharmais. Analisis asupan dilakukan dengan food frequency questionnaire semikuantitatif dan 24-hours food recall. Pemeriksaan asam amino serum dengan metode spektofotometri, Sel T helper-17 dengan metode flowcytometry, dan C-reactive protein dengan metode latex agglutination, serta kadar IL 17, IL 6 dan TNFα dengan metode ELISA. Data yg didapat kemudian di analisis dengan uji T atau Mann Whitney untuk melihat hubungan dan untuk menganalisis hubungan dalam tabel digunakan uji Chi-Square atau Fischer Exact, sedangkan untuk korelasi digunakan uji Pearson atau Spearman. Asam amino triptofan, asparagin, glutamin, valin, lisin dan sistein berkorelasi positif dengan sitokin anti-inflamasi dan status nutrisi, sebaliknya negatif dengan sitokin pro inflamasi. Asam amino fenilalanin, treonin, dan glutamat berkorelasi positif dengan sitokin pro-inflamasi dan berkorelasi negatif dengan status nutrisi dan sitokin anti inflamasi. Khusus aspartat, selain berkorelasi positif dengan sitokin pro inflamasi, juga berkorelasi positif dengan indeks massa tubuh, tetapi menunjukkan korelasi negatif dengan penurunan berat badan. Beberapa asam amino serum terbukti berhubungan dengan status sitokin dan status nutrisi pada subjek kanker paru dengan kaheksia, sehingga perlu menjadi perhatian dalam terapi nutrisi pasien kanker
Kata kunci: asam amino serum, status nutrisi, sitokin, kaheksia kanker

ABSTRACT
Cancer patients generally experience weight loss associated with cancer cachexia. The pathophysiology of cancer cachexia is multifactorial, including the effects of pro inflammatory cytokines and systemic inflammation.. The plasma amino acid profile was found to significantly undergo changes in cancer patients. Protein depletion can occur due to decreased intake or direct effects of tumors on protein metabolism. This study aimed to determine the profile and relationship between serum amino acids, nutritional status and pro-anti-inflammatory cytokines, and T helper 17 cells in lung cancer cachexia patients. This cross-sectional study with consecutive sampling in lung cancer patients with cachexia took subjects over the age of 18 years and who had not been treated or who had finished therapy for more than 2 months at the Dharmais Cancer Hospital. Dietary intake analyses were carried out with semiquantitative food frequency questionnaire and 24-hour food recalls. Blood tests were carried out in the form of serum amino acids, cytokines, C-reactive protein and T helper 17 cells. Data obtained were then analyzed by the T or Mann Whitney test to see the relationship and to analyze relationships in the table used chi-square or Fischer Exact, while for correlation used Pearson or Spearman test. The amino acids tryptophan, asparagine, glutamine, valine, lysine and cysteine were positively correlated with anti-inflammatory cytokines and nutritional status, and negatively correlated with pro-inflammatory cytokines. Phenylalanine, threonine and glutamate amino acids were positively correlated with pro-inflammatory cytokines and negatively correlated with nutritional status and anti-inflammatory cytokines. Aspartate showed a positive correlation pro inflammatory cytokines and body mass index, but a negative correlation with weight loss. Some serum amino acids have been shown to be related to cytokines and nutritional status in lung cancer cachexia patients, so it should be a concern in nutritional therapy for cancer patients"
Depok: Fakultas Kedokteran Universitas Indonesia, 2019
D-Pdf
UI - Disertasi Membership  Universitas Indonesia Library
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Nadya Johanna
"ABSTRAK
Pendahuluan: Malaria merupakan masalah kesehatan global dengan angka kesakitan dan kematian yang tinggi. Namun, sampai saat ini, mekanisme imunitas terhadap malaria asimtomatik masih belum dimengerti secara jelas sehingga sistem kontrol malaria pun belum berhasil dikembangkan.Tujuan: Meneliti hubungan status malaria asimtomatik dengan konsentrasi IL-10, TNF-?, dan IFN-? pada penduduk di Kecamatan Nangapanda, Nusa Tenggara Timur.Metode: Penelitian ini menggunakan data sekunder dari studi ldquo.

ABSTRACT
Does treatment of intestinal helminth infections influence malaria? Background and methodology of a longitudinal study of clinical, parasitological and immunological parameters in Nangapanda, Flores, Indonesia ImmunoSPIN Study rdquo;. Data dianalisis dengan uji Mann-Whitney SPSS versi 20.0 .Hasil: Dari 116 sampel, prevalensi malaria asimtomatik sebesar 11,2 . Konsentrasi IL-10, TNF-?, dan IFN-? pada kelompok status malaria asimtomatik positif: 29,36 pg/ml; 3,20 pg/ml; dan 111,89 pg/ml; pada kelompok status malaria asimtomatik negatif: 21,74 pg/ml; 3,20 pg/ml; dan 1,60 pg/ml. Tidak ditemukan adanya perbedaan bermakna antara status malaria asimtomatik dengan konsentrasi IL-10 dan TNF-? p > 0,05 , namun terdapat kecenderungan adanya perbedaan bermakna dengan konsentrasi IFN-? p = 0,051 .Kesimpulan: Tidak terdapat hubungan yang bermakna antara status malaria asimtomatik dengan konsentrasi IL-10 dan TNF-? pada penduduk di Kecamatan Nangapanda, Nusa Tenggara Timur, namun terdapat kecenderungan adanya hubungan bermakna dengan konsentrasi IFN-?.
Introduction Malaria is a global health problem. However, the immune mechanism of asymptomatic malaria has not been clearly understood. Thus, an effective malaria control system is still unavailable.Aim To analyze the association between asymptomatic malaria status and IL 10, TNF , and IFN concentration among residents in Nangapanda District, East Nusa Tenggara Province which is malaria endemic.Method This study uses secondary data from ldquo Does treatment of intestinal helminth infections influence malaria Background and methodology of a longitudinal study of clinical, parasitological and immunological parameters in Nangapanda, Flores, Indonesia ImmunoSPIN Study rdquo . Data were analyzed using Mann Whitney SPSS version 20.0 .Result From 116 samples, the prevalence of asymptomatic malaria was 11.2 . The IL 10, TNF , and IFN concentration on positive asymptomatic malaria residents were 29.36 pg ml 3.20 pg ml and 111.89 pg ml on negative asymptomatic malaria residents were 21.74 pg ml 3.20 pg ml and 1.60 pg ml. There were no significant differences between asymptomatic malaria status and IL 10 and TNF concentration p 0.05 , however, there was a tendency of a significant difference with IFN concentration p 0.051 .Conclusion No significant associations between asymptomatic malaria status and IL 10 and TNF concentration were found. However, there was a tendency of a significant association with IFN concentration."
2017
S-Pdf
UI - Skripsi Membership  Universitas Indonesia Library
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Osamu Kaminuma
"Abstrak
Eosinophilic inflammation in combination with immunoglobulin E (IgE) production is a characteristic feature of atopic dermatitis. Although activated T-helper type (Th) 2 cells play critical roles in the local accumulation and activation of eosinophils, whether they induce eosinophilic skin inflammation, independent of the IgE-mediated pathway has been unclear. To address the functional role of T cells in allergic skin diseases, we herein transferred Th1/Th2-differentiated or naive DO11.10 T cells into unprimed BALB/c mice. Ovalbumin-specific Th2 cells, as well as eosinophils, accumulated in the skin upon antigen challenge, despite the absence of antigen-specific IgE. Neither antigen-specific Th1 nor naive T cells induced eosinophil accumulation, although Th1 cells by themselves migrated into the skin. Interleukin (IL)-4, IL-5, and eotaxin were specifically produced in the skin of antigen-challenged, Th2 cell-transferred mice, whereas interferon (IFN)-γ and regulated on activation, normal T cell expressed and secreted (RANTES) were preferentially produced in Th1 cells-transferred mice. Production of monocyte chemoattractant protein (MCP)-1 and MCP-3 was enhanced by both Th1 and Th2 cells. The accumulation of eosinophils and Th2 cells in the skin was suppressed by both dexamethasone and FK506, indicating an essential role of Th2 cells in eosinophil recruitment. We conclude that Th2 cells can induce eosinophilic infiltration into the skin in the absence of antigen-specific IgE."
Suwon Korea: The Korean Academy of Asthma, Allergy and Clinical Immunology, 2018
610 AAIR 10:1 (2018)
Artikel Jurnal  Universitas Indonesia Library
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Angky Budianti
"COVID-19 merupakan penyakit penyebab pandemi pada akhir 2019. Perbedaan manifestasi klinis pada infeksi SARS-CoV-2 ini memicu banyak pertanyaan di kalangan peneliti dan medis. Perbedaan klinis COVID-19 tersebut dapat dipicu oleh faktor hospes, patogen maupun lingkungan. Infeksi SARS-CoV-2 terutama melalui saluran napas atas, tempat kolonisasi mikroba komensal dan patogen. Bagaimana interaksi antara mikroba yang berkolonisasi dengan SARS-CoV-2 dalam menimbulkan respons inflamasi di saluran napas atas masih belum diketahui dengan jelas. Penelitian ini bertujuan menganalisis hubungan antara karakteristik mikrobiota, serta rasio kadar sitokin pro- dan anti-inflamasi dari saluran napas atas dengan beratnya COVID-19.
Penelitian ini merupakan studi potong lintang menggunakan 74 swab nasofaring dan orofaring di dalam viral transport medium (VTM) dari pasien COVID-19 berusia 18–64 tahun. Profil mikrobiota di saluran napas atas dan kadar IL-6, IL-1β, IFN-γ, TNF-α dan IL-10 diperiksa dengan metode sekuensing 16S ribosomal RNA dan Luminex assay, secara berurutan. Selanjutnya dilakukan analisis hubungan antara beratnya COVID-19 dengan OTU, keragaman alfa dan beta dari mikrobiota saluran napas atas.
Lima filum terbanyak di saluran napas pasien COVID-19 di Indonesia berusia 18-64 tahun adalah Firmicutes (32,3%), Bacteroidota (27,1%), Fusobacteriota (15,2%), Proteobacteria (15,1%) dan Actinobacteria (7,1%). Analisis indeks Shannon dan ACE menunjukkan bahwa tidak ada penurunan keragaman microbiota saluran napas atas dengan bertambah beratnya penyakit. Namun, ada perbedaan bermakna keragaman beta pada mikrobiota saluran napas atas antara COVID-19 ringan dan berat. Keberlimpahan filum Firmicutes (p = 0,012), dan genus Streptococcus (p = 0,033) dan Enterococcus (p = 0,031) lebih tinggi pada COVID-19 berat dibandingkan yang ringan, sedangkan keberlimpahan filum Fusobacteriota (p = 0,021), Proteobacteria (p = 0,030), Campilobacterota (p = 0,027), genus Neisseria (p = 0,008), dan Fusobacterium (p = 0,064), spesies Porphyromonas gingivalis (p = 0,018), Fusobacterium periodonticum (p = 0,001) dan Fusobacterium nucleatum (p = 0,022) lebih tinggi pada COVID-19 ringan dibandingkan berat. Keberadaan bakteri Prevotella buccae (p = 0,005) dan Prevotella disiens (p = 0,043) lebih rendah pada COVID-19 berat. Rasio TNF-α/IL-10 lebih tinggi pada COVID-19 berat (p < 0.05). Selanjutnya, rasio IL-6/IL-10, IFN-γ/IL-10, dan IL-1β/IL-10 juga lebih tinggi pada COVID-19 berat, namun tidak berbeda bermakna jika dikaitkan dengan beratnya penyakit.
Penelitian ini mendukung adanya hubungan antara karakteristik mikrobiota di saluran napas atas dengan beratnya COVID-19 pada pasien dewasa. Studi lebih lanjut diperlukan untuk memeriksa mekanisme bagaimana mikrobiota mencegah beratnya COVID-19. Rasio TNF-α/IL-10 dari saluran napas dapat menjadi prediktor beratnya penyakit dan sebagai alternatif pemeriksaan kadar sitokin pada COVID-19 yang kurang invasif dibandingkan serum.

COVID-19 is a disease that caused a pandemic at the end of 2019. Clinical manifestations difference in SARS-CoV-2 infection has raised many questions in research and medical provider. The clinical differences in COVID-19 can be triggered by host, pathogen and environmental factors. SARS-CoV-2 mainly enters through the upper airway, with colonization of commensal and pathogenic microbes. How the interaction between colonized microbes and SARS-CoV-2 in causing an inflammatory response in the upper airway is still not clearly known. Therefore, we examined the association between the diversity of microbiota, pro- and anti-inflammatory cytokines ratio of upper respiratory and COVID-19 severity.
This research is an observational cross-sectional study using 74 nasopharyngeal and oropharyngeal swabs in viral transport medium from COVID-19 patients aged 18-64 years. We examined microbiota profile in the upper airway using 16S ribosomal RNA sequencing method and levels of IL-6, IL-1β, IFN-γ, TNF-α and IL-10 were examined by Luminex assay. We also examined the association between COVID-19 severities with OTU analysis, alpha and beta diversity of upper respiratory microbiota.
The top five phyla in upper respiratory tract of Indonesian COVID-19 patients with aged of 18–64 years old were Firmicutes (32,3%), Bacteroidota (27,1%), Fusobacteriota (15,2%), Proteobacteria (15,1%) and Actinobacteria (7,1%). Shannon and ACE index analysis showed no decline of microbiota diversity in upper airway with the increase of disease severity. However, there were significant differences of beta diversity in the upper airway microbiota between mild and severe COVID-19. The abundance of the Firmicutes phylum (p = 0,012), Streptococcus (p = 0,033) and Enterococcus (p = 0,031) genera were significantly higher in severe COVID-19 than mild, while the abundance of the Fusobacteriota (p = 0,021), Proteobacteria (p=0,030), and Campilobacterota (p = 0,027) phyla, Neisseria (p = 0,008), and Fusobacterium (p = 0,064) genera, Porphyromonas gingivalis (p = 0,018), Fusobacterium periodonticum (p = 0,001) and Fusobacterium nucleatum (p = 0,022) species were significantly higher in mild. The presence of Prevotella buccae (p=0.005) and Prevotella disiens (p=0.043) bacteria was lower in severe COVID-19. The TNF-α/IL-10 ratio was significantly higher in severe COVID-19 (p < 0.05). Furthermore, IL-6/IL-10, IFN-γ/IL-10, and IL-1β/IL-10 ratio was also higher in severe, but those were not significantly related to the disease severity.
This research supports the relationship between the severity of COVID-19 and microbiota diversity in the upper airway in adults. Further studies are needed to examine the mechanism by which microbiota prevents the COVID-19 severities. The ratio of TNF-α/IL-10 from upper airway swab may be as a predictor of disease severity and alternative for examining cytokine levels in COVID-19 which is less invasive than serum.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
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UI - Disertasi Membership  Universitas Indonesia Library
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Ellyza Nasrul
"Aim: To investigate the expression CD4+ T cell and CD8+ T cell as well as TNF-a and INF-7 level on Citron ic hepatitis C.
Methods: This is a cross-sectional study. Forty patients with chronic hepatitis C based on laboratory examination, who were collected from blood transition centers at Dn M. Djamil Hospital. The control group used forty healthy samples.
Results: There were 40 chronic hepatitis C cases satisfying the inclusion criteria. We found that CD4+ T cells count 50.35 + 3.1 8%; CD8+ T cells count 59.37 + 3.52%; TNF-a level 22.03 :t 3.?2 pg/ml and INF-7 level 4.47 + 1.47 pg/ml.
Conclusion: The chronic infection hepatitis C virus have given the effects on the immunocompetent cells which increased of CD4+, CD8+, TNF-a level and INF-y level."
Jakarta: The Indonesian Journal of Gastroenterology Hepatology and Digestive Endoscopy, 2006
IJGH-7-2-Agt2006-33
Artikel Jurnal  Universitas Indonesia Library
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