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The HuIFN-alpha and beta genes were examined by the PCR method in the 11 human lymphoblastoid cell lines. The results showed that the homozygous deletion of HuIFN-alpha and beta genes was detected in 5 of 11 cell lines and in 5 of 11 cell lines, respectively. The deletions of both the HuIFN-alpha and beta genes were observed in 4 of 11 cell lines. One T cell leukemia cell line deleted only HuIFN-alpha gene, while the other T cell leukemia line deleted only HuIFN-beta gene. This suggests that the deletions of HuIFN-alpha and beta genes may be related the development of leukemia or lymphoma.

Human T lymphoblastoid cell (RPMI 8402 cell) produced interferon (IFN) through the induction by Sendai virus. The priming effect on the interferon production in the RPMI 8402 cell could be found by the pretreatment of human leukocyte IFN (Hu IFN-alpha), but not by that of the IFN produced in the RPMI 8402 cell (T-IFN). The superinduction by the irradiation of ultraviolet rays or the treatment of antimetabolites (actinomycin D and cycloheximide) or 5-bromodeoxyuridine was not found. The T-IFN was completely neutralized by the anti-Hu IFN-beta serum, but not by the anti-Hu IFN-alpha serum at all. In conclusion, it was confirmed that the IFN produced in the RPMI 8402 cell through the induction by Sendai virus was antigenically identical to Hu IFN-beta.

Human leukocyte interferon (HL-IF) enhanced the growth inhibition of tumor cells by the human peripheral leukocytes. There was a dose relation between the enhancement of the growth inhibition of tumor cells and the antiviral activity of interferon. When the ratio of lymphocyte to tumor cell was 10:1 or 50:1, it was recognized that HL-IF enhanced the growth inhibition of tumor cells by lymphocyte. The heterologous IFs--mouse and rabbit IFs--or heat-inactivated or trypsinized IF did not enhance the growth inhibition of tumor cells by lymphocytes. RNase treatment did not reduce the antiviral activity and the growth inhibition.

The target cells (KB, HeLa, FL, human hepatoma and murine L929) were cocultured with human embryonic fibroblasts in the Petri dish. The degenerative changes of the target cells except L929 cells by the human fibroblasts were found. Human leukocyte interferon (HuIFN-alpha) and human fibroblast interferon (HuIFN-beta) enhanced these changes, but mouse IFN (MuIFN-alpha, beta) did not. The other human fibroblasts also caused the degenerative changes of the target cell, and HuIFN-alpha enhanced these changes. It was concluded that human fibroblasts play a certain role in the suppression of the human tumor cell.

The culture supernatant of human fibroblasts caused degenerative changes in the target cells. This tumor degenerating factor in the supernatant (TDF) appeared already on the 1st day of culture and increased gradually to the 8th day. TDF was effective on human KB, HeLa, FL and of hepatoma cells, but neither on murine L929, 3T3, SV-3T3 cells nor MDBK cells. Furthermore, TDF was not effective on human non-transformed cells, namely various human fibroblasts. Human leukocyte interferon (HuIFN-alpha) enhanced TDF production. The coculture of human fibroblasts with KB cells augmented TDF production.

The preparations of interferon or virus-inhibiting factor produced in L cell (L-IF) and mouse brain (MB-IF) enhanced the killing of Staphylococcus aureus (S.a.) by the mouse peritoneal macrophage. The L-IF, heat-inactivated at 80 degrees or 60 degrees for 30 min., and mock L-IF could not enhance the killing of S.a. The heterologous human and rabbit interferon preparations didn't enhance the bactericidal activity of macrophage. The L-IF didn't have any effect on the release of lysozyme from the macrophages.

Tumor-degenerating factor (TDF) with the specific activity of 2.9 units/mg of protein was produced and purified by several chromatographies. The specific activity was increased to 302 units/mg of protein by DEAE-Sephadex A-50 chromatography, repeated twice. Then, this preparation was purified to the specific activity of 2,040 units/mg of protein with recovery rate of 16.6% by Con A-Sepharose and CM-Sephadex C-50 chromatographies. Finally, the specific activity was increased to 9,010 units/mg of protein with the final recovery rate of 14.6% by Blue Sepharose CL-6B chromatography.

The authors clarified the characteristics of effector cells of which inhibitory activity against the tumor cell growth was enhanced by interferon (IF). These cells adhered to nylon wool, but they did not adhere to a glass surface. They showed the EA-rosettees formation, but they did not show the E-rosett formation. This activity was diminished by trypsinization, X-ray irradiation and treatment with hydrocortisone and progesterone. It was not changed by the addition of aggregated Ig. In summary, the effector cells in the present study could not be identical to NK cells.

To make it possible to measure the interferon-alpha (IFN-alpha) producing capacity in a great number of healthy donors and patients, we developed the simple method (the whole blood method). For the measurement of the IFN-producing capacity, the heparinized blood was incubated with Sendai virus at 37 degrees C for 20 hours. The IFN activity of the culture supernatants was determined by the cytopathic effect inhibition assay. We measured the IFN-producing capacity in 531 healthy donors and 130 cancer patients. The results showed that the IFN-producing capacity in cancer patients was significantly lower than that in healthy donors. Although there were individual variations in the IFN-producing capacity, no age and sex differences were observed. These results indicate that this method is useful for the measurement of IFN-producing capacity in human.

Human leukocyte interferon preparation (HuIFN-alpha LE) was given to the patients with cancer or with chronic hepatitis. Spontaneous tumor cell growth inhibition by human peripheral lymphocytes (STGI) and NK activity were enhanced by the systemic administration of HuIFN-alpha LE, although there were differences in the kinetics between the two activities after one time administration or by the repeated administration. This suggests that IFN acts indirectly on the tumor cells by the medium of normal lymphocytes or NK cells, and that tumor cell growth inhibition is different from NK activity.

Human leukocyte interferon (HL-IF) enhanced the NBT reduction of human peripheral neutrophil in vitro. Dose relation between IF activity and the NBT reduction was recognized. Heat-inactivated HL-IF, HL-IF neutralized by anti-IF serum or heterologous IF could not increase the NBT reduction.

Effects of preheating and injection of cis-DDP (CDDP) or interferon on tumor-induced sensitization to systemic hyperthermia (SH) was investigated in mice. LD50 of SH at 42.0 +/- 0.2 degrees C (core body temperature) was 43 min in normal mice and 8 min in mice which were i.p. transplanted with FMA3 cells at a dose of 10(5) one day before. In mice which had received the SH for 10 min one hour before, one hour after or one day before the transplantation, LD50 of the SH one day after the transplantation was 41, 35 and 22 min, respectively. An injection of CDDP given i.p. at a dose of 4 mg/kg one day after the transplantation, which was effective to kill about 99% of the tumor cells, did not change the course of thermosensitization after the transplantation. An i.p. injection of mouse interferon did not change the thermosensitivity of normal mice, but greatly suppressed the thermosensitizing effect of tumor cells when it was given one day before the transplantation.

There are two antigenic types of human virus-induced interferons (IFNs): one is a human leukocyte IFN (Hu IFN-alpha and the other is a human fibroblast IFN (Hu IFN-beta). We examined the antigenic types of IFNs produced in several human T and B lymphoblastoid cell lines through the induction by Sendai virus. We could produce IFNs in the several human T lymphoblastoid cells (RPMI 8402, Peer, JM and CCRF-CEM) and in several human B lymphoblastoid cells (BALL-1, B35M, DG-75 and ARH-77), and examined antigenic types of the IFNs produced. The results showed that all T lymphoblastoid cells produced Hu IFN-beta. On the other hand, the antigenic types of IFN were dependent on each cell line in human B lymphoblastoid cell lines. The IFN produced in BALL-1 cell was only one type of Hu IFN-alpha. The IFNs produced in ARH-77 and DG-75 cells contained two types of the Hu IFN-alpha and Hu IFN-beta. The IFN produced in B35M cell was only one type of Hu IFN-beta. It was concluded that human T lymphoblastoid cell produced Hu IFN-beta, and that the first type of human B lymphoblastoid cell produced only Hu IFN-alpha, the second type produced Hu IFN-alpha and Hu IFN-beta and the third type produced only Hu IFN-beta.