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Human TNF-α

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Function

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that plays a central role in systemic inflammation and is a key mediator of the acute phase response. Originally identified for its ability to induce tumor necrosis, TNF-α is now recognized as a pleiotropic cytokine with diverse functions in immunity, inflammation, apoptosis, and cellular proliferation. It is primarily produced by activated macrophages, though many other cell types can produce TNF-α under inflammatory conditions.

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Biological Functions

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Inflammatory Responses

  • Acute Inflammation: Initiates and amplifies inflammatory cascades
  • Endothelial Activation: Promotes expression of adhesion molecules and chemokines
  • Leukocyte Recruitment: Attracts neutrophils, monocytes, and lymphocytes to sites of inflammation
  • Fever Induction: Acts as an endogenous pyrogen

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Immune System Modulation

  • Macrophage Activation: Enhances antimicrobial and tumoricidal activities
  • T Cell Activation: Provides costimulatory signals for T cell proliferation
  • B Cell Function: Modulates antibody production and class switching
  • NK Cell Activity: Enhances natural killer cell cytotoxicity

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Pathological Roles

  • Autoimmune Diseases: Excessive TNF-α drives pathology in rheumatoid arthritis, Crohn’s disease, psoriasis
  • Sepsis: Contributes to septic shock and multiple organ failure
  • Cancer: Dual role as both tumor promoter and suppressor
  • Neuroinflammation: Involved in neurodegenerative diseases

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Target Details

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Therapeutic Relevance

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Anti-TNF Therapies

TNF-α is one of the most successful therapeutic targets in modern medicine:

  • Monoclonal Antibodies: Infliximab, adalimumab, golimumab, certolizumab pegol
  • Soluble Receptors: Etanercept (TNFR2-Fc fusion protein)
  • Clinical Applications: Rheumatoid arthritis, ankylosing spondylitis, psoriasis, Crohn’s disease, ulcerative colitis
  • Market Impact: Multi-billion dollar market for TNF inhibitors

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Research Applications

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Drug Development

  • Inhibitor Screening: Identifying new TNF-α antagonists
  • Biosimilar Development: Developing generic versions of anti-TNF biologics
  • Next-Generation Therapeutics: Improved selectivity and reduced side effects
  • Combination Therapies: TNF blockade with other immunomodulatory agents

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Biomarker Studies

  • Disease Activity: TNF-α levels correlate with disease severity in many conditions
  • Treatment Monitoring: Tracking therapeutic response to anti-TNF therapy
  • Drug Levels: Measuring therapeutic antibody concentrations
  • Immunogenicity: Detecting anti-drug antibodies

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Basic Research

  • Inflammatory Mechanisms: Understanding TNF-α signaling pathways
  • Disease Models: Studying TNF-α in animal models of human disease
  • Cellular Biology: TNF-α effects on different cell types
  • Immune Regulation: Role in adaptive and innate immunity

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Clinical Applications

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Established Indications

  • Rheumatoid Arthritis: First and most successful application
  • Inflammatory Bowel Disease: Crohn’s disease and ulcerative colitis
  • Psoriasis: Both skin and joint manifestations
  • Ankylosing Spondylitis: Spinal inflammation and stiffness

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Emerging Applications

  • Uveitis: Inflammatory eye disease
  • Hidradenitis Suppurativa: Chronic skin condition
  • Behçet’s Disease: Multi-system inflammatory disorder
  • COVID-19: Potential role in cytokine storm management

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Safety Considerations

  • Infection Risk: Increased susceptibility to bacterial and viral infections
  • Malignancy: Potential increased cancer risk with long-term use
  • Autoimmunity: Paradoxical development of autoimmune conditions
  • Cardiovascular: Effects on heart failure and cardiovascular risk

TNF-α plays crucial roles in host defense against infections. Anti-TNF therapies can significantly increase infection risk, particularly for tuberculosis and other opportunistic infections. Careful patient screening and monitoring are essential.

TNF-α is available in our target library as both the full-length trimer (most biologically relevant) and as monomeric forms for specialized applications. The trimeric form is recommended for most binding studies as it represents the physiologically active state.