# DEVELOPMENTAL BIOLOGY OF IMMUNO REGULATORY CYTOKINES

> **NIH NIH K11** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 1994 · $82,620

## Abstract

The overall objectives of this proposal are: 1) to use basic science
techniques to assess the mechanisms regulating production and utilization
of immunoregulatory cytokines in infected fetal and neonatal subjects,
and 2) based on this biology, to devise and test new cytokine-based
treatments for newborn infants with infectious diseases.  The studies
will proceed through four stages, each represented by a specific aim.
They are:

1) To describe the kinetics of production of various immunoregulatory
cytokines from explanted cells of various types, as well as in vivo, from
fetal and newborn mice and from fetal and newborn humans.  Our initial
studies indicate that explanted macrophages from preterm neonates
generate less than 1/10th the quantities of G-CSF and IL-6 as do
macrophages from adults, and that this is the result of decreased
transcription.

2) To determine the mechanism responsible for the diminished production
of certain cytokines by fetal and newborn mice and humans.  We propose
two alternative hypotheses; that fetal cytokine-producing cells are
environmentally "programmed" to produce certain cytokines well and others
poorly, vs an intrinsic defect in fetal cytokine-producing cells.
Studies are proposed that will first, determine which of the alternative
hypotheses is correct and second, begin to elucidate the responsible
mechanism.

3) To assess the actions on target cells from newborn infants of the
specific cytokines that are produced poorly by newborn infants.  We
maintain that reduced production of certain cytokines (such as G-CSF) by
infected fetal subjects must be interpreted in light of information on
the action of such cytokines on fetal target cells.

4) To assess the effect of administering the specific cytokines that are
produced poorly by infected newborn infants, to infected newborn mice and
newborn humans.  Experimental animal models of neonatal bacterial
infection with E. coli and group B streptococcus are in use in our
laboratory.  In addition, we have begun phase I and II trials of
administration of recombinant human G-CSF to infected human neonates.

## Key facts

- **NIH application ID:** 2194523
- **Project number:** 5K11HD001006-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **SAM.gov UEI:** LL8GLEVH6MG3
- **Principal Investigator:** KURT R SCHIBLER
- **Activity code:** K11 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $82,620
- **Award type:** 5
- **Project period:** 1993-01-01 → 1997-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194523

## Citation

> US National Institutes of Health, RePORTER application 2194523, DEVELOPMENTAL BIOLOGY OF IMMUNO REGULATORY CYTOKINES (5K11HD001006-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194523. Licensed CC0.

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