Old Tuberculin Associated with Liposomes: A New Interferon Inducer

Abstract

Old tuberculin (OT) does not induce interferon in mice while OT associated with liposomes made to contain a positive charge (L⁺:OT) induced high titers of circulating interferon. Since OT associated with neutral or negatively charged liposomes did not induce interferon, the positive charge of the liposome is therefore important. Dose-response studies indicated the optimum inducer contains 50 mg OT. Kinetic studies indicated that the peak interferon response occurred 4 hours after induction with L⁺:OT. Sonication in the preparation of L⁺:OT was also important since mixing of sonicated positively charged liposomes (L⁺s) with sonicated OT(OTs) induced interferon titers 10-fold less than L⁺:OT prepared by sonication of OT and liposomes together. L⁺s or OTs injected alone did not induce interferon. L⁺s injected before or after OTs did not induce interferon. Interferon induced by L⁺:OT was characteristic of virus-induced interferon by the following criteria: (a) stable at pH 2, (b) inactivated by trypsin, (c) inactivated at 56°C for 30 min, and (d) neutralized by rabbit antisera to mouse L cell interferon. Thus, the association of a noninducer or a weak interferon inducer with liposomes may result in potent interferon inducers. Many nontoxic, low molecular weight agents may thus be of value by association with liposomes to induce interferon for antiviral and antitumor therapy.