# REGULATION OF INTERFERON PRODUCTION

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 1990 · $242,306

## Abstract

The major thrust of our research during the last several years has been the
detailed characterization of novel "interferon" mRNA species induced by
poly(I) poly (C) in diploid human fibroblasts:  a 1.3 kb "interferon-beta2"
species and a 1.8 kb "interferon-beta3" species.  The cytokine, to which we
originally applied the name "interferon-beta2" and which is now called
"interleukin-6," has emerged as a major systemic alarm signal produced in
response to tissue injury.  IL-6 phosphoglycoproteins (size range 23-30
kDa) in turn affect the function of a wide variety of different cell types.
IL-6 elicits major changes in the biochemical, physiological and
immunological status of the host (e.g. the "acute phase" response.)  We
have developed a broad research program which has already provided key
insights into the structure and function of human IL-6.  We propose to
continue this effort in the following areas:

I.  MOLECULAR BIOLOGY:  The hallmark of IL-6 gene regulation is the
induction of the gene in many different tissues by inflammation-association
cytokines (IL-1), TNF, PDGF, other IFNs).  We plan to conduct detailed
investigations of the following:  cis-acting regulatory DNA elements in the
IL-6 promoter and trans-acting wild-type and mutant transcription factors
involved in the regulation of this gene, particularly focusing on the 23-bp
MRE identified by us; tissue-specificity of IL-6 induction and the
molecular events that lead to constitutive vs. inducible expression of IL-
6.

II.  BIOCHEMISTRY:  Different tissues secrete multiple forms of IL-6 which
are post-translationally modified.  We plan to characterize these
modifications; characterize the biochemical nature of IL-6 in human body
fluids (particularly the 45 kDa IL-6 complex) and carry out structure-
activity studies of natural and recombinant IL-6 proteins.

III.  CELL BIOLOGY:  IL-6 regulates expression of specific genes in several
different target, cells.  We propose to explore the effects of IL-6, alone
and in combination with IL-1, TNF and IFN-gamma, on plasma protein
secretion by hepatocytes, monocytes and fibroblasts; characterize the novel
IL-6 "receptor" mRNA species found in fibroblasts and investigate the
inhibition of epithelial cell proliferation by IL-6.

IV.  PATHOPHYSIOLOGY:  High IL-6 levels are found in plasma and body fluids
in acute inflammatory disease states.  We shall investigates the
significance of altered IL-6 levels (systemic and local) in patients with
acute and chronic infections, neoplasia and autoimmune diseases; and
explore the association between IL-6 haplotypes and specific disease
states.

## Key facts

- **NIH application ID:** 3126618
- **Project number:** 2R01AI016262-12
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **SAM.gov UEI:** LHGDNJMZ64Y1
- **Principal Investigator:** PRAVIN B SEHGAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $242,306
- **Award type:** 2
- **Project period:** 1979-09-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126618

## Citation

> US National Institutes of Health, RePORTER application 3126618, REGULATION OF INTERFERON PRODUCTION (2R01AI016262-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126618. Licensed CC0.

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