# A single oral dose of an iso-alpha acids rich hop extract dampens the lipoteichoic acid mediated immune response of monocytes in healthy individuals

## TL;DR

A single dose of hop extract reduces immune responses triggered by bacterial components in healthy individuals.

## Contribution

This study demonstrates that iso-alpha acids from hops can modulate immune responses to bacterial lipoteichoic acid in humans.

## Key findings

- 15 mg of IAA reduced LTA-induced IL-6 and IL-1β secretion in PBMCs compared to placebo.
- IAA suppressed JNK-mediated inflammatory signaling in vitro without affecting TLR2 activation.

## Abstract

Bacterial infections significantly contribute to global mortality. Lipoteichoic acid (LTA), a key component of Gram-positive bacterial cell walls, triggers immune responses via Toll-like receptor 2 (TLR2). Iso-alpha acids (IAA), bitter compounds derived from hops (Humulus lupulus L.), are known for their anti-inflammatory properties, but their effects on human immune modulation remain unclear. This study explored the effect of a single oral dose of IAA on LTA-induced inflammatory responses in human immune cells and underlying molecular mechanisms.

In a pilot study in healthy female volunteers (n = 5) dose- and time-dependent effects (0–90 mg IAA) on LTA-induced immune responses in monocytes were assessed. A randomized, placebo-controlled cross-over study (n = 13, male and female) evaluated the acute effects of 15 mg IAA. Peripheral blood mononuclear cells (PBMCs) were stimulated with LTA ex vivo, and cytokine release (IL-6, IL-1β) was measured. Mechanistic studies using J774A.1 cells and TLR2-transfected HEK293 cells explored the molecular pathways of IAA.

In the pilot study, 15 mg IAA was identified as the most tolerated dose in terms of taste for the participants which still had a marked effect on LTA-mediated IL-6 release from monocytes. In the main study, PBMCs from IAA-treated participants showed significantly lower IL-6 and IL-1β secretion after LTA stimulation compared to placebo (p < 0.05). In vitro, IAA suppressed JNK-mediated inflammatory signaling without affecting TLR2 activation.

A single low-dose intake of IAA from hops reduces LTA-induced cytokine release in blood immune cells, likely via JNK inhibition, suggesting its potential role in modulating inflammatory responses.

The online version contains supplementary material available at 10.1007/s00394-026-03931-x.