TNFα (mouse) (Tumor necrosis factor-alpha, mouse)

Biology and Diseases

Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine with cytotoxic activity that is primarily produced by macrophages. TNFα is involved in systemic inflammation and is a member of the group of cytokines that stimulate the acute phase reaction. When administered to animals or humans it causes inflammation, fever, cardiovascular effects, hemorrhage, coagulation, and acute phase responses similar to those seen during acute infections and shock states. By promoting the inflammatory response, TNFα is associated with many autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, psoriasis, and refractory asthma. TNFα also plays a role in cancer and regulates apoptotic cell death, cellular proliferation, differentiation, tumorigenesis, and

viral replication.

Therapies

Autoimmune disorders can be treated with TNFα-inhibitors, which act as anti-inflammatory agents. This inhibition can be achieved with a monoclonal antibody such as infliximab (Remicade) or adalimumab (Humira), or with a circulating receptor fusion protein such as etanercept (Enbrel). Modifications of the TNFα pathway may also have potential for treatment or prevention of some cancers; however, TNFα-inhibitors have also been implicated in the development of childhood leukemia.

Unmet Need

The broad involvement of inflammation in human disease ensures

that TNFα will remain an attractive therapeutic target for autoinflammatory diseases like rheumatoid arthritis and Crohn’s disease, as well as other diseases like cancer, Alzheimer’s, AIDS, tuberculosis, and insulin resistance. This presents a need to accurately quantify TNFα during preclinical and early phase drug development. In particular, there is a need for a more sensitive mouse TNFα assay that accurately quantifies mTNFα in very small volumes of mouse serum to enable long-term, time-lapse monitoring of mice.

Singulex Answer

The Singulex Mouse TNFα assay, optimized for use on the Erenna System, provides the sensitivity to quantify subpicogram levels of mTNFα in small volumes of serum (<100 μL). The precision of the mTNFα assay enables measurement of mTNFα velocity, providing valuable information on drug efficacy and disease progression. The mTNFα assay has an LoD of 0.1 pg/mL and a reading range of 0.1 to 2000 pg/mL, providing accurate quantification of mTNFα in only 20 μL of plasma. This assay will allow investigators to:

1. Measure the efficacy and dosing of therapies that interfere with the inflammatory response, such as TNFα inhibitors.

2. Perform robust preclinical studies in mice when mTNFα concentration is used as a therapeutic endpoint.

3. Quantify mTNFα in very small volumes of mouse serum to enable long-term, time-lapse monitoring of mice.

Application Note

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