INFLAMMATORY CYTOKINES INDUCE AIDS-KAPOSIS SARCOMA-DERIVED SPINDLE CELLS TO PRODUCE AND RELEASE BASIC FIBROBLAST GROWTH-FACTOR AND ENHANCE KAPOSIS SARCOMA-LIKE LESION FORMATION IN NUDE-MICE

Homosexual males often present signs of immune activation and are like ly to have increased levels of inflammatory cytokines such as IL-1 bet a, TNF-alpha, and IFN-gamma. These individuals develop Kaposi's sarcom a (AIDS-KS) more frequently than other HIV-1-infected groups. Our prev ious work demonstrated that inflammatory cytokines stimulate the growt h of spindle cells derived from AIDS-KS lesions (AIDS-KS cells) and th at these cells produce high levels of bFGF that mediate autocrine and paracrine (endothelial) cell growth and angiogenesis. Here we show tha t AIDS-KS cells constitutively produce and release bioactive bFGF in t he absence of cell death, and that extracellular bFGF exist in both a soluble and a bound form; the latter can be released by treatment with trypsin, heparin, or heparinase I. Inflammatory cytokines stimulate b oth the synthesis and release of biologically active bFGF from KS cell s and enhance their ability to induce angiogenic KS-like lesions in nu de mice. Because bFGF is highly expressed in primary KS lesions, and i s a mediator of KS-like lesion formation, these results suggest that t he export of bFGF induced by inflammatory cytokines may play a critica l role in the induction and progression of KS in HIV-1-infected homose xual men.