TABLE 3.
Potential clinical relevance of reductions in key endogenous physiological proteins after exposure in vitro to a specified 3-protease blend14–16,30–32
| ENDOGENOUS PROTEIN | EFFECT OF 3-PROTEASE FORMULATION* | POTENTIAL CLINICAL RELEVANCE (TOPICAL APPLICATION) |
|---|---|---|
| TNF alpha (monomeric, trimeric) | Reduction | Expressed by multiple cell types and involved in several pro-inflammatory and proliferative processes; works in concert with IL-1; increase in dendritic cells involved in immune response. Reduction may soften the intensity of inflammation induced by impairment of SC and in association with several dermatoses. |
| IL-1 (IL-1 beta) | Reduction | Increased early with SC permeability barrier damage (increased TEWL) and several dermatological disorders; pro-inflammatory via signaling release of other cytokines, growth factors, and recruitment of T cells; upregulates adhesion molecules; enhances epidermal a differentiation; works in concert with TNF-α. Reduction may soften the magnitude of inflammation induced by impairment of SC and in association with several dermatoses. |
| IL-6/IL-6R | Reduction | An early pro-inflammatory cytokine which contributes to amplification of inflammation (with contribution from TNF-α and IL-1); modulates the activation, differentiation, and growth of T cells; functional regulation of T, NK, and B cells. Reduction may soften early inflammation and amplification loop through reduction of IL-6, IL-1, and TNF-α. |
| IL-4 | Reduction | Promotes proliferation of activated mature T cells and cytotoxic properties; suppresses Th1 cytokine pattern; upregulated in atopic dermatitis (Th2 pattern); enhances IgE receptor expression, mast cell growth, and contributes to IgE production. Reduction may ameliorate inflammation patterns associated with atopic skin. |
| IL-2 | Reduction | “T cell growth factor” essential for developing immune response, the proliferation and clonal expansion of activated T cells, and regulation of T cell function in Th1-mediated diseases (i.e., psoriasis). Reduction may diminish the intensity of inflammation associated with response patterns observed with inflammatory skin changes and disease states. |
| MMPs | Reduction (some MMPs) | MMPs modulate/degrade dermal matrix; some induce other inflammatory cascades; increased or involved in several skin disorders (i.e., rosacea, acne) |
| MMP-1 (collagenase) | Reduction | Degradation of fibrillar collagen (collagenolysis) |
| MMP-3 (gelatinase) | Reduction | Degradation of type IV collagen and gelatin |
| MMP-9 (stromelysin) | Reduction | Degradation of several extracellular matrix proteins (not fibrillar collagen). Reduction may soften degradation of dermal matrix and inflammatory pathways signaled by specific MMPs. |
| Substance P | Reduction | Neuropeptide involved in mediation of nocioception and pain; involved in axon reflex- mediated vasodilation, wheal-flare reaction, and neurogenic inflammation; increased levels in association with eczema (atopic dermatitis and pruritus. Reduction can decrease symptomatology and edema associated with inflammatory skin disorders. |
*
3-protease blend: bromelain, ficin, actinidin
TNF=tumor necrosis factor; IL=interleukin; MMPs=matrix metalloproteinases