# Anti-inflammatory drug target to reduce adverse pregnancy outcomes.

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $703,958

## Abstract

Abstract
Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor and fetal inflammation leading to
injury responses in fetal organs such as the brain, lung and the GI tract. However, the mechanisms and
precise therapeutic approaches remain elusive largely because of lack of relevant animal models. We have
developed a powerful new model of intrauterine infection in preterm Rhesus macaques: Intraamniotic (IA)
injection of live E. coli followed 24h later with antibiotics. This model results in persistent IUI. Importantly, the
maternal and fetal inflammation persists despite clearance of E. coli bacteremia, resulting in preterm labor
(PTL), fetal immune aberrations and fetal neuroinflammation. We now propose validating IL1 as a drug target
for IUI induced prematurity and fetal inflammation. This grant is based on our data that Anakinra (IL1 receptor
antagonist used clinically for rheumatoid arthritis) significantly decreased neutrophilic infiltration at the
maternal-fetal interface and amniotic fluid IL6, PGE2 in a different but widely used model of IA LPS.
Furthermore, Anakinra reversed the LPS-induced “inflammatory Treg” in the fetal spleen. We propose to test
the hypothesis that Anakinra will reduce the residual maternal and fetal inflammation in infectious models that
closely simulate IUI in pregnant women with two Aims. In Aim 1, we will ask if anti IL1 directed anti-
inflammatory therapy will decrease intrauterine infection induced inflammation and preterm labor. We will use
state-of-the-art single-cell transcriptomic approach to unravel cellular and molecular mechanisms of
inflammation at the maternal-fetal interface, define labor associated pathways of IUI that are responsive to IL1
inhibition. Using multi-parameter flow cytometry, we will identify mechanisms of neutrophil recruitment and
activation in the chorio-decidua. In Aim 2, We will identify mucosal and systemic fetal immune perturbations
resulting from transient bacteremia and sterile fetal inflammation. We will determine if Anakinra can reduce
fetal systemic inflammation and neuroinflammation resulting from IUI. These studies will develop the critical
knowledge base for future studies aimed at repurposing of Anakinra as a novel anti-inflammatory therapy for
human IUI. A collaborative multi-disciplinary team will use high-resolution immunology, genomics/proteomics,
neuro-science, and translational approaches in modeling IUI and fetal inflammation in an animal model that
closely mimics the human pathology.

## Key facts

- **NIH application ID:** 10147740
- **Project number:** 5R01HD098389-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** SUHAS KALLAPUR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $703,958
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147740

## Citation

> US National Institutes of Health, RePORTER application 10147740, Anti-inflammatory drug target to reduce adverse pregnancy outcomes. (5R01HD098389-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147740. Licensed CC0.

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