HUMAN ACOUSTIC NEUROMAS SECRETE INTERLEUKIN-6 IN CELL-CULTURE - POSSIBLE AUTOCRINE REGULATION OF CELL-PROLIFERATION

INTERLEUKIN-6 (IL-6) SECRETION by cell cultures of human acoustic neur omas was examined. Secretory rates varied from 0.02 to 5.4 ng/10(5) ce lls per 4 days, depending on the tumor. The IL-6 immunoreactivity elut ed from a Sephadex G-100 column in a major peak corresponding to an M( r) of 30,000 and a lesser peak corresponding to an M(r) of 50,000. Wes tern blot analysis revealed three IL-6 immunoreactive bands with M(r)s corresponding to 53,000, 29,000, and 24,000. Tumor necrosis factor-al pha, interleukin-1-beta, and cholera toxin all stimulated IL-6 secreti on. An antisense phosphorothioate oligonucleotide against IL-6 messeng er RNA inhibited both [H-3]thymidine uptake and IL-6 secretion by acou stic neu roma cells in culture. In addition, [H-3]thymidine uptake was inhibited by a specific polyclonal antibody against IL-6. We conclude that human acoustic neuroma cells produce and secrete IL-6, which may act in an autocrine manner to stimulate cellular proliferation.