Regulation of interleukin 1 production by α||||||||+ β||||||||interferons : evidence for both direct and indirect enhancement

Author

Robert Victor Candler

Date of Award

12-1984

Degree Type

Thesis

Degree Name

Master of Science

Major

Microbiology

Major Professor

Robert N. Moore

Committee Members

Ted McDonald, Barry Rouse

Abstract

Pretreatment of murine macrophages with interferon (IFN) influences a variety of their responses to other mediators. For example, bone marrow derived macrophage progenitors pretreated with IFN α + β display augmented proliferation upon subsequent exposure to specific macrophage-type colony-stimulating factor (M-CSF). Similar pretreatment of macrophage-enriched cultures from proteose-peptone elicited peritoneal exudate cells results in enhanced- production of the immunoregulatory polypeptide interleukin 1 (lL-1) in response to lipopolysaccharide (LPS). Therefore, the present investigation was performed to determine if exposure of mature murine exudate macrophages and macrophage cell line cultures would, in addition, augment M-CSF stimulated IL-1 production. The results indicate that preincubation with IFN α + β enhances IL-1 production in response to M-CSF as well as to LPS. This pretreatment regimen elicited enhanced macrophage responsiveness to sub—optimal doses of CSF as well as LPS.

LPS hyporesponsive cells from C3H/HeJ mice or CSF hyporesponsive P388Di monocytic tumor cells produced an apparently synergistic level of IL-1 in response to the two stimuli combined. Prior exposure to IFN α + β enhanced this apparently synergistic response.

An unexpected finding in this investigation was that IFN α + β pretreatment dosages exceeding 1000 U/ml directly stimulated IL-1 production by exudate macrophages. Direct and augmented stimulation of IL-1 production by IFN α + β could be neutralized by addition of highly specific anti IFN α + β antiserum or by heat treating the preparation at 56°C for 45 minutes.

There is a correlation between the local presence of IFN and both inflammation and fever. This observation is discussed in regard to the IFN enhanced production of IL-1.

Recommended Citation

Candler, Robert Victor, "Regulation of interleukin 1 production by α||||||||+ β||||||||interferons : evidence for both direct and indirect enhancement. " Master's Thesis, University of Tennessee, 1984.
https://trace.tennessee.edu/utk_gradthes/14590