Induced proteins in human peripheral mononuclear cells over a range of clinically tolerable doses of interferon-gamma

Journal of Interferon Research
D M PaulnockE C Borden

Abstract

This study assessed biologic response modification at three different dose levels (0.15, 1.5, and 15 mg/m2) of interferon-gamma (IFN-gamma) administered by intravenous bolus three times weekly. A final total of 24 patients were evaluable. Dose-limiting toxicity occurred at the highest dose level (15 mg/m2) and included fatigue, leukopenia, and hepatotoxicity. Evaluation of biologic response modification included assessment of 2',5'-oligoadenylate (2-5A) synthetase activity in peripheral mononuclear cells, measurement of serum beta 2-microglobulin and expression of beta 2-microglobulin on monocytes, measurement of monocyte HLA Class II expression (HLA-DR, HLA-DQ), and measurement of hydrogen peroxide generation by monocytes 24 h after the first and fourth IFN-gamma treatments. Significant increases (p less than 0.05) from baseline were seen at 24 h with all parameters except H2O2 generation. Except for enhancement of HLA-DR, even the lowest dose (0.15 mg/m2) augmented synthesis of 2-5A synthetase and HLA proteins. A dose-response effect was noted for changes in serum and monocyte beta 2-microglobulin levels but not for 2-5A synthetase levels or HLA Class II antigen expression on monocytes. After 4 doses administered over 9 days,...Continue Reading

References

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Citations

Jan 1, 1992·Clinical Immunology and Immunopathology·E C Borden
Sep 27, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Ernest C Borden

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