EFFECT OF CYTOKINES ON THE SECRETION OF THE 5TH AND 8TH COMPLEMENT COMPONENTS BY HEPG2 CELLS

Liver cells can be induced by interleukin-1, tumor necrosis factor and interleukin-6 to secrete higher amounts of complement components. Inf ormation, so far available only for the early components, indicates th at these cytokines exhibit different effects on various complement pro teins. For instance, they promote the biosynthesis of C3 and B but hav e no effect on that of C4 and C2. These observations led us to evaluat e the ability of interleukin-1, tumor necrosis factor and interleukin- 6 to modulate the secretion of the late complement components by HepG2 cells, a human hepatoma-derived cell line known to produce several co mplement proteins. The amount of complement components in the culture supernatant was evaluated by a sensitive enzyme-linked immunosorbent a ssay revealing picogram levels of these proteins. The HepG2 cells were found to secrete a substantial amount of C3 (approximately 1 mug/10(6 ) cells), easily detectable C5 (approximately 150 ng/10(6) cells) and C8 (approximately 10 ng/10(6) cells) and a low amount of C6 (approxima tely 0.5 ng/10(6) cells), whereas the levels of both C7 and C9 could n ot be measured. The addition of interleukin-1, tumor necrosis factor a nd interleukin-6 to the cell culture resulted in an enhanced secretion of C8, whereas that of C5 was only marginally increased. None of thes e cytokines had a clear effect on the secretion of C6 nor induced the production of C7 and C9. The magnitude of increased levels of C3 and C 8 in the culture medium was related to the cytokine used, since interl eukin-6 induced a more substantial response of C8 than interleukin-1, and, conversely, interleukin-1 was more effective than interleukin-6 i n enhancing the secretion of C3. No clear differences were found in th e amount of the various components secreted in response to tumor necro sis factor.