Chapter 234. Immunobiologicals, Cytokines, and Growth Factors in Dermatology

Recombinant interferons

Interferon-α and Interferon-γ

• Enhances cell-mediated cytotoxicity against viral disease and malignancy via promotion of MHC expression and suppression of Th2 cytokine production

• Variable

Recombinant Interleukins and growth factors

Interleukin 2

• Maintains helper T-cell populations
• Enhances natural killer cell cytotoxicity and lymphokine activated cell activity

• Variable

Interleukin 1 receptor antagonist

• Blocks the interaction between IL1 and its receptor
• Suppresses IL1 mediated inflammatory responses (e.g., leukocyte recruitment, osteoclast activation)

• Variable

Granulocyte-macrophage colony-stimulating factor

• Promotes the proliferation and differentiation of myeloid precursors

• Variable

Platelet-derived growth factor

• Promotes wound healing via angiogenic activity and proliferative effects on fibroblasts and smooth muscle cells

• Daily application of gel to affected site

Antibody-based therapeutics

Anti-TNF-α

• Infliximab: chimeric monoclonal antibody; neutralizes both membrane-bound and soluble TNF-α
• Adalimumab: human monoclonal antibody; neutralizes both membrane-bound and soluble TNF-α

• 5-mg/kg IV at week 0, 2, and 6, then q8wk 80-mg SC followed by 40-mg SC 1 week later, then 40-mg SC qow
• 80 mg SC followed by 40 mg SC 1 week later, then 40 mg SC qow

Anti-IL12/IL23

• Ustekinumab: human monoclonal antibody; inhibits IL-12 and IL-23 mediated inflammatory processes

• Patients <100 kg: 45-mg SC followed by same dose at week 4, and q12wk thereafter
• (Patients >100 kg: receive 90 mg)

Anti-LFA-1

• Efalizumab: humanized monoclonal antibody; interferes with lymphocyte activation, cytotoxicity, and trafficking to the skin; withdrawn from US market in 2009 because of PML

• 0.7-mg/kg SC followed by 1 mg/kg qwk

Anti-CD20

• Rituximab: chimeric monoclonal antibody; promotes a reduction in CD20+ cells (B-cells)

• Variable

Fusion proteins

Alefacept

• Human IgG1 Fc region fused to LFA-3 extracellular domain; interferes with T-cell activation by blocking the interaction between LFA-3 and CD2

• 15 mg IM qwk for 12 weeks

Etanercept

• Human IgG1 Fc region fused to TNF type II receptor domain; neutralizes soluble TNF-α

• 50-mg SC biw for 12 weeks, then 50-mg SC qwk

Denileukin Diftitox

• Diphtheria-toxin component fused to IL2; promotes apoptosis of T-cells expressing the high affinity IL2 receptor, CD25

• Variable