Effects of interleukin-1 and interleukin-1 receptor antagonist in AIDS-Kaposi's sarcoma.

Kaposi's sarcoma (KS) is the most common tumor seen in patients with HIV-1 infection. HIV-1 may induce KS directly through viral protein(s) or indirectly through regulation of cytokines such as IL-1 and IL-6. We have shown that AIDS-KS spindle cells express IL-1 beta and that IL-1ra inhibits KS-spindle cell growth. IL-1ra had little effect on human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells (HASM), and human foreskin fibroblast (NN41). These findings support an autocrine activity for IL-1. Furthermore, exogenous IL-1 can enhance AIDS-KS cell growth, and this effect is completely blocked by IL-1ra. As expected, IL-1ra also blocks IL-1 mediated upregulation of IL-6 and bFGF, both of which are autocrine growth factors for KS. IL-1ra is thus a potential candidate for the treatment of AIDS-associated KS.