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

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.