Human Biologic Response Modification by Interferon in the Absence of Measurable Serum Concentrations: A Comparative Trial of Subcutaneous and Intravenous Interferon-beta serine

Abstract

The effect on a range of biologic responses of interferon-beta serine (IFN-beta ser), administered by either the sc or the iv route, was examined in 16 patients. Despite the absence of IFN in the serum of 13 of 16 patients after sc administration, biologic changes associated with IFN administration occurred. Significant increases in peripheral mononuclear cell surface proteins were evident. Monocyte human leukocyte antigen-DR (HLA-DR) showed a 23% increase in mean fluorescent intensity (P = .04) and a 9% increase in percentage of positive cells (P = .02); lymphocyte OKT10 had an 11% increase in percentage of positive cells (P less than .0001) and a 26% increase in mean fluorescent intensity (P = .002). Natural killer cell activity against the Change target increased by 125% (P = .004). Intracellular activity of 2',5'-oligoadenylate synthetase increased 297% at 24 hours and 226% at 48 hours (P less than .0001). Significant increases in serum concentrations of beta 2 microglobulin (24% at 24 hr and 27% at 48 hr, P less than .0001) and neopterin (85%, P = .0001 and 165%, P = .00001) were observed. These alterations after sc administration were similar quantitatively to those resulting from the same dose of IFN-beta ser given iv. Thus, serum IFN concentrations did not have to be measurable for IFN-beta ser to exert biologic activity. The different effects of two dose levels, 45 X 10(6) IU and 180 X 10(6) IU, also were compared independent of route. The higher dose resulted in greater increases over baseline of 2',5'-oligoadenylate synthetase activity (344% vs. 145% at 24 hr; 231% vs. 83% at 48 hr) and serum neopterin concentrations (185% vs. 99% at 24 hr; 271% vs. 153% at 48 hr). For all the other parameters, there was no significant difference between the two doses.

Mesenchymal Stem Cells Overexpressing IFN-β Inhibit Breast Cancer Growth and Metastases through Stat3 Signaling in a Syngeneic Tumor Model

“…Because of IFN-β's well described short half life [43], it is not expected that sufficient levels of injected recombinant IFN-β can be maintained at the tumor site to affect tumor growth before the protein is degraded. However, using MSC to secrete IFN-β in situ would overcome this issue.…”

Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-α/β–inducible gene expression, without significant toxicity

“…Both 2Ј5Ј OAS and neopterin are at least as sensitive as enzyme-linked immunosorbent assay (ELISA) detection of serum interferon. 34 …”

Immunological monitoring of azathioprine treatment in multiple sclerosis patients

“…NK activity and the percentage of circulating peripheral blood NK cells have not been clearly related to MS [23,30,38]; however, on the assumption that viral infections might play a role at least in the triggering of disease exacerbations [25], therapy with interferon β (IFN-β) has recently been adopted [15]. IFN-β has a boosting effect on NK activity [11].A number of reports have suggested that IFN-γ [2] and tumour necrosis factor alpha (TNF-α) production [6], interleukin 2 (IL-2) or sIL-2R levels [1] are related to the clinical activity of the disease. Both TNF-α and IFN-γ are detected in MS lesions, suggesting a role in inflammatory demyelination [4,33].…”