Tumor Necrosis Factor (TNF) its types and Advance Research on TNF

Tumor necrosis factors (or the TNF family) refer to a group of cytokines that can cause cell death (apoptosis). TNF is primarily produced as a 212-amino acid-long type II transmembrane protein arranged in stable homotrimers. It is produced chiefly by activated macrophage and  by many other cell types such as CD4+ lymphocytes, NK cells, neutrophils , mast cells, eosinophils , and neurons. 

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                                The primary role of TNF is in the  regulation of immune cells. It has been implicated in the pathogenesis of a wide spectrum of human diseases, including sepsis, diabetes, cancer, osteoporosis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases. The interaction of TNF with TNF receptor–1 (TNF-R1) activates several signal transduction pathways.

TYPE OF TUMOR NECROSIS FACTOR (TNF)

TNF α

1. It is also known as cachectin,
2. Produced by macrophages and Mast cells.
3. TNF alpha is a  inflammatory cytokine. 
4. Target tissue: tumor cells and Inflammatory cells.
5. Responsible for extensive weight loss (cachexia) associated with chronic inflammation.
6. TNF α Receptor - TNFR1 (TNF receptor type 1; CD120a; p55/60)

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TNF β

1. Also called lymphotoxin
2. Produced by TH1 and Tc cells
3. Target tissue: tumour cells and macrophage and neutrophils.
4. TNF beta has cytotoxic activity and Enhances the phagocytic activity.
5. Inhibited by interleukin 10
6. TNF β Receptor- TNFR1 and TNFR2 (TNF receptor type 2; CD120b; p75/80).

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TNF ANTAGONIST

ADVANCE PHARMACOLOGY / RECENT RESEARCH OF TUMOR NECROSIS FACTOR (TNF)

Tumor necrosis factor-alpha-converting enzyme activities and tumor-associated macrophages in breast cancer (Sep 2013)-   

• The role of the tumor micro environment especially of tumor-associated macrophages (TAMs) in the progression and metastatic spread of breast cancer is well established.
• The key roles of immunomodulatory cytokines released by tumor cells, including colony-stimulating factor 1, tumor necrosis factor (TNF) and soluble TNF receptors 1/2.
• Importantly, these factors are released through ectodomain shedding by the activities of the tumor necrosis factor-alpha-converting enzyme (TACE/ADAM17). The role of TACE activation leading to autocrine effects on tumor progression has been extensively studied.
• TACE inhibitors, currently in clinical trials, will certainly affect TAMs and subsequently treatment outcomes based on the substrates it releases.
• Recent studies shows, the potential roles of TACE  ectodomain shedding in the breast tumor microenvironment are reviewed with a focus on the release of tumor-derived immunomodulatory factors shed by TACE that directs TAM phenotypes and functions.

Role of  TNF Inhibitors in  Ankylosing Spondylitis (June 2014)

• Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with an increased risk of osteoporosis and fractures. TNF inhibitors have been used to treat AS, but their effect on bone is unclear.
• Thus,  a meta-analysis conducted  to study the effect of TNF inhibitors on spine and hip BMD in patients with Ankylosing Spondylitis.
• TNF inhibitors can increase lumbar spine and total hip BMD and maintain femoral neck BMD for up to 2 years in patients with AS.
• More research is needed to assess the effect of TNF inhibitors on bone quality and fracture risk.

TNF-α regulates miRNA targeting mitochondrial complex-I and induces cell death in dopaminergic cell   (MARCH 2015)

• Tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine is elevated in blood, CSF and striatum region of the brain in Parkinsonism patients .
• The cells treated with low dose of TNF-α for prolonged period induce cell death . TNF-α alters mitochondrial complex-I activity, decreases adenosine triphosphate (ATP) levels, increases reactive oxygen species levels and mitochondrial turnover through autophagy.
• TNF-α differentially regulates miRNA expression involved in pathogenesis of PD.
• Recent study shows TNF-α is a potential regulator of miRNAs which may regulate mitochondrial functions and neuronal cell death, having important implication in pathogenesis of Parkinsonism disease.

Risks for opportunistic tuberculosis infection in a  patients with inflammatory bowel disease receiving a tumor necrosis factor-α inhibitor (March2015)

• Real-world epidemiological data on tuberculosis (TB) infection in patients with inflammatory bowel disease (IBD) receiving TNF-α inhibitors are scarce.
• Recent studies investigate  the risks for and case characteristics of TB in a large cohort of IBD patients treated with TNF-α inhibitors in Korea.
• TNF-α inhibitor treatment strikingly increases the risk of TB infection in an IBD population from a TB endemic area.
• Continuous evaluation of the development of de novo TB infection in IBD patients subjected to long-term TNF inhibitor therapy is mandatory.

Four cases of Japanese patients with psoriatic arthritis in whom effective treatments by anti-tumor necrosis factor-α drugs were evaluated by magnetic resonance imaging together with improvement of skin lesions (2014)

• Psoriatic  skin lesions of psoriatic arthritis (PsA) usually precede the onset of joints pain. The purpose of this study was to elucidate the effectiveness of MRI in the evaluation of anti-TNF-α drugs on joint disease of Japanese PsA patients.
• Data were collected from four adult Japanese male PsA patients. MRI of the affected hand was performed at baseline and 1–7 months after infliximab or adalimumab treatment.
• T1-weighted gadolinium-enhanced images with fat suppression were acquired in the coronal, sagittal and/or axial planes. Recent studies shows the apparent improvement of synovitis, periarticular inflammation, tenosynovitis and/or bone marrow edema by MRI after anti-TNF-α treatments in all the patients together with the improvement of skin lesions.
• This imaging enables dermatologists and radiologists to assess and monitor early inflammatory changes, and to grant PsA patients earlier access to modern treatment.

Nano anti-tumor necrosis factor-alpha based potentiometric sensor for tumor necrosis factor-alpha detection (2014)

• Tumor necrosis factor (TNF)-α promotes rheumatoid arthritis (RA) symptoms, including inflammation and bone erosion.
• The role of TNF-α in RA is considered to be complex because cytokine is responsible for a wide-range of functions, such as activation of immune cells, stimulation of osteoclast differentiation, and induction of cellular apoptosis.
• It has appeared that the determination of TNF-α concentration in serum might be helpful in the staging and prognosis of diseases.
• In Recent study, a simple and sensitive potentiometric sensor method has described for the determination of TNF-α in serum.
• The sensor has exhibited a visibly enhanced response. The sensor has demonstrated a quick and reliable response, ability to be reproduced, as well as long-term stability.