Figure 6. Model of inflammation and lymphedema.

Loss of lymphatic vascular integrity leads to diminished lymph transport, which promotes both edema and inflammation. TNF-α, a potent mediator of inflammation, is also a known inducer of the pro-lymphangiogenic factor, VEGF-C. Both ketoprofen and pegsunercept have general inhibitory effects on inflammation, ketoprofen promotes endogenous repair mechanisms mediated by VEGF-C and VEGFR-3by simultaneous inducing TNF-α. In contrast, pegsunercept directly inhibits TNF-α and therefore exacerbates the disease state by disrupting pro-lymphangiogenic processes driven by VEGF-C and VEGFR-3.