COMPARISON OF CONSTITUTIVE CYTOKINE RELEASE IN HIGH AND LOW HISTOLOGIC GRADE AIDS-RELATED KAPOSIS-SARCOMA CELL STRAINS AND IN SERA FROM HIV+ KS+ AND HIV+/KS+ PATIENTS/

Kaposi's sarcoma (KS) is both an AIDS-defining disease and the most co mmon HIV-associated malignancy. A cytokine-mediated pathogenesis for A IDS-KS is implicated because AIDS-KS-derived cell strains both respond to and express a variety of cytokines. We have reported the establish ment of several (n = 18) AIDS-KS cell strains and determined that redu ced exogenous growth factors are necessary to sustain proliferation in isolates from high histologic grade KS lesions. This current investig ation explored the possibility that there are histologic grade-associa ted differences in either the qualitative and/or quantitative constitu tive release of AIDS-KS growth stimulatory cytokines. Our findings sho wed that the incorporation of HTLV-II cytokine-rich conditioned media induced both qualitative and significant quantitative cytokine release , suggesting that exogenous growth promoters stimulate constitutive cy tokine release. ELISA of our AIDS-KS cell strains demonstrated constit utive release of IL-6 (seven of seven), FGF-2 (five of seven), GM-CSF (three of seven), and IL-1 beta (one of seven). None of our AIDS-KS ce ll strains constitutively released detectable levels of Onco-M, IL-4, PDGF, TNF-alpha, or TNF-beta. In addition, we report that the method o f cytokine result quantitation significantly affects reported cytokine levels. We determined that there was no significant histologic grade- dependent difference in the constitutive release of soluble cytokines by in vitro grown cultures of AIDS-KS cells. The presence of HIV influ enced the sera cytokine profiles by elevating IL-6 and decreasing PDGF concentrations of HIV+ individuals relative to HIV- healthy controls. However, the presence of KS was not associated with unique serum cyto kine profiles, because no differences were noted in comparisons of HIV +/KS+ versus HIV+/KS- individuals. Our findings suggest that the local environment is key in modulating AIDS-KS cytokine expression and that KS growth-promoting factors function at the local or paracrine, not t he systemic, level. In conclusion, our previous results demonstrated a histologic grade-associated difference in the in vitro growth capacit y of AIDS-KS cells; with high histologic grade isolates displaying a m arked growth advantage during culture in minimally supplemented media. Findings from this current study reveal that although the potential f or a constitutive growth loop exists in the high-grade isolates, it is not reflected in the free levels of soluble cytokines secreted into t he culture medium.