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Neonatal lipopolysaccharide administration causes long-term changes in mouse immunosteroids.

Melody Salehzadeh1,2, Anna Mazurenko2,3, Kiran K Soma1,2,3,4

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American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|January 7, 2026
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Early infections in mice impact adult immune systems by altering steroid hormone levels within lymphoid organs. This suggests local immunosteroid production may explain lasting immune effects from early-life stress.

Keywords:
cortisoldevelopmentearly-life adversitysepsisstress

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Area of Science:

  • Immunology
  • Endocrinology
  • Neuroscience

Background:

  • Early-life infections can permanently alter immune and endocrine system development.
  • Glucocorticoids (GCs) are key stress hormones produced by adrenal glands and lymphoid organs (immunosteroids).

Purpose of the Study:

  • To investigate the long-term effects of early-life lipopolysaccharide (LPS) exposure on glucocorticoid and mineralocorticoid regulation in adult mice.
  • To determine if early-life LPS challenge influences steroid hormone levels and gene expression in blood and lymphoid tissues in adulthood.

Main Methods:

  • Neonatal mice received LPS or saline (first hit), followed by adult LPS or saline administration (second hit) in a 2x2 design.
  • Steroid levels in blood and lymphoid organs (bone marrow, thymus, spleen) were measured using liquid chromatography-tandem mass spectrometry.
  • Gene expression of steroidogenic enzymes, steroid receptors, and HPA axis components was analyzed via RT-qPCR.

Main Results:

  • Early-life LPS exposure did not significantly alter adult blood GC levels.
  • However, early-life LPS increased corticosterone and 11-dehydrocorticosterone in lymphoid organs of adults receiving a second LPS hit.
  • Aldosterone levels were differentially affected in blood and lymphoid tissues based on sex and subsequent LPS challenge, with increased steroidogenic enzyme gene expression (CYP11B2) observed.

Conclusions:

  • Early-life infections can lead to lasting alterations in local steroid hormone production within lymphoid organs.
  • Elevated local glucocorticoid and aldosterone synthesis in lymphoid tissues may mediate the enduring effects of early-life infections on immune function.