IL10 is a potent modulator of IL1-mediated inflammation in bovine endometrial explants

Bovine uterine inflammation impairs fertility, animal welfare and economics. Balanced regulation of interleukin-1 family proteins is crucial to resolve endometrial inflammation.

mRNA expression of interleukin 1B (IL1B) and its receptor antagonist (IL1RA) was examined in bovine endometrial explants.

Endometrial explants from 26 cows were incubated with heat-inactivated pathogenic Escherichia coli, opportunistic Bacillus pumilus or commensal and potentially protective Lactobacillus buchneri (3, 14 and 24 h) and with cytokines (24 h; IL1B, IL17A, IL10). mRNA expression of IL1B and IL1RA was quantified via reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and mixed effects models were used for statistical analysis.

IL1B mRNA expression increased after bacterial challenge at all timepoints (P < 0.001). IL1RA mRNA expression increased after Escherichia coli and Bacillus pumilus exposure only at 3 h, but after Lactobacillus buchneri at 14 and 24 h (P < 0.010). A pro-inflammatory shift of the IL1RA:IL1B ratio was detected at all timepoints and for all bacterial challenges (P < 0.020). Stimulation with IL10 reduced IL1B and IL1RA mRNA expression and shifted the IL1RA:IL1B ratio in an anti-inflammatory direction (P < 0.001).

This study confirmed explant culture as a suitable model for analyzing inflammatory regulation in the bovine endometrium and identified IL10 as a potent modulator of endometrial IL1B and IL1RA.

Not only Escherichia coli and Bacillus pumilus, but also unexpectedly Lactobacillus buchneri, induced initial pro-inflammatory mRNA expression patterns to be different depending on culture duration. This highlights the need for further research on pathogenic and opportunistic versus potentially protective bacteria in bovine uterine health.