Serum Immune Proteins in Limb Lymphedema Reflecting Tissue Processes Caused by Lymph Stasis and Chronic Dermato-lymphangio-adenitis (Cellulitis).

Background: Lymphedema of limbs affects a large mass of tissues. Pathological changes develop in skin and subcutaneous tissue. Bacterial retention in edema fluid is followed by chronic inflammatory reaction. The question arises whether the chronic processes affecting a large mass of limb tissues are reflected in the serum by appearance of specific proteins accumulating and subsequently absorbed from the lymphedematous tissues Aim: To measure the concentration of serum proteins (1) participating in cellular disintegration such as caspase 1, sFas, high-mobility group box 1 (HMGB1), and serpin, (2) cell growth regulating factors such as cortisol, human growth hormone, keratinocyte growth factor, and insulin-like growth factor (IGF), and (3) angiogenic and growth factors such as angiopoetins 1 and 2, adiponectin, leptin, and transforming growth factor beta.

Results: We found (1) increased concentration of serum caspase 1, sFas, serpin, and HMGB1 accounting for cellular destruction, (2) raised levels of cortisol and IGF, confirming active cellular processes, and (3) elevated concentrations of angiopoetin 1, adiponectin, and leptin, indicating proliferation of adipose tissue.

Conclusions: Proteins appearing in serum in high concentrations in patients with lymphedema without systemic clinical and biochemical signs of inflammation indicate that multiple processes of destruction and rebuilding proceed in the lymphedematous tissues. Measuring concentration of caspase 1, sFas, serpin, HMGB1 protein, adiponectin, and leptin give insight into these processes. Lymphedema should be considered as tissue process characterized not only by increase in mobile tissue fluid volume but also tissue restructuring. Compression and drainage therapy should be complemented by anti-inflammatory medication.