Biologic Effects and Basic Science of a Novel Immune-Modulation Therapy

The immune system is a system of dynamic equilibrium, with inflammatory responses (mediated by T helper type 1 cells, interleukin [IL]-1β, interferon-γ, and tumor necrosis factor-α [TNF-α]) being balanced by anti-inflammatory responses (mediated by T regulatory type 1 cell, T helper type 3 cells, IL-4, IL-10, and transforming growth factor-β). Therefore, neutralization of inappropriate inflammatory cytokines is a therapeutic strategy that has been attempted in many chronic inflammatory conditions, mostly targeting TNF-α, using either monoclonal antibodies or modified receptor proteins (etanercept). There is functional redundancy among the inflammatory cytokines. For example, in addition to TNF-α, both IL-1β and IL-6 are elevated in patients with chronic heart failure (CHF); thus neutralizing the activity of TNF-α alone may be an inadequate approach in this patient group. Immune-modulation therapy (IMT) results in downregulation of proinflammatory cytokine levels and upregulation of anti-inflammatory cytokines. This alteration in the balance between proinflammatory and anti-inflammatory cytokines may be more appropriate than neutralizing the activity of a single cytokine in the treatment of conditions such as CHF. Several animal studies investigating the effect of IMT in inflammatory conditions including allergic contact hypersensitivity, ischemia reperfusion injury, and atherogenesis are reviewed.