The soluble form of the IL-6 receptor (sIL-6Rα) is a potent growth factor for AIDS-associated Kaposi's sarcoma (KS) cells; the soluble form of gp130 is antagonistic for sIL-6Rα-induced AIDS-KS cell growth

Kaposi's sarcoma (KS) is most frequently associated with HIV-infected individuals (AIDS-KS). While AIDS-KS-derived spindle cells (AIDS-KS cells) contribute to the development of KS lesions, growth regulation of these cells in vivo is poorly understood. AIDS-KS cells express considerable amounts of the signal transducing subunit (gp130) of the IL-6 receptor, but only a scanty amount of its binding subunit (IL-6R alpha). This phenotype can account for the lack of IL-6 responsiveness of AIDS-KS cells. We now report that the soluble form of IL-6R alpha (sIL-6R alpha), lacking transmembrane and cytoplasmic regions, functions as a potent growth factor for AIDS-KS cells by making these cells responsive to IL-6. After exposure to sIL-6R alpha together with IL-6 in culture, AIDS-KS cells assumed a spindle-shaped morphology and showed a remarkable augmentation of growth, while IL-6 alone did not induce AIDS-KS cell growth. Even without the addition of IL-6, sIL-6R alpha induced significant growth levels of AIDS-KS cells. Since AIDS-KS cells express high levels of IL-6, it is likely that, in the presence of sIL-6R alpha, these cells acquire an IL-6 autocrine growth loop. Anti-gp130 antibodies blocked the action of sIL-6R alpha on AIDS-KS cells; hence, we refer to sIL-6R alpha as a gp130-related AIDS-KS cell growth factor. In contrast, the soluble form of gp130 (sgp130) had inhibitory effects on AIDS-KS cell growth, thereby suggesting that a complex regulatory system is involved in the modulation of the gp130-mediated AIDS-KS cell growth. In recent years, soluble forms of IL-6R alpha and gp130 have been detected in the sera of healthy individuals and increased levels of sIL-6R alpha as well as IL-6 have been noted in the sera of HIV-infected patients. It seems reasonable to assume that perturbed production of sIL-6R alpha and sgp130 may play a crucial role in the development and regression of AIDS-KS lesions by directly acting on growth of KS cells through the gp130-mediated pathway.