On the other hand, high-dose intravenous administration of IL-2, e.g. for treatment of malignant melanoma and metastatic renal carcinoma, frequently causes severe adverse reactions dominated by capillary leak syndrome, hypovolemia and accumulation of fluid in the extra-vascular space along with organ failure [46], which is caused by an IFN-γ and TNF-α dominated ‘cytokine storm’ and thus limits its clinical use [47]. Here, TNF is linked to melanoma.