Associations between male testosterone and immune function in a pathogenically stressed forager-horticultural...

Area of Science:

• Human evolutionary biology
• Immunology
• Endocrinology

Background:

• High endogenous testosterone offers fitness advantages but may incur costs.
• Testosterone's trade-off with somatic maintenance, particularly immune function, is debated.
• Previous studies on testosterone and immunity yield mixed results due to methodological limitations.

Purpose of the Study:

• To investigate the association between endogenous testosterone and immune responses.
• To examine cytokine profiles before and after antigen stimulation in men.
• To explore testosterone's role in immune investment trade-offs.

Main Methods:

• Analyzed 13 circulating cytokines in 109 Tsimane men (aged 40-89) using a Milliplex panel.
• Measured urinary testosterone via enzyme immunoassay.
• Stimulated whole blood samples ex vivo with phytohemagglutinin (PHA) and lipopolysaccharides (LPS).

Main Results:

• Higher testosterone was linked to down-regulated cytokine responses after PHA stimulation (T-cell biased).
• No significant association was found between testosterone and cytokine responses after LPS stimulation (B-cell mediated).
• Men with higher testosterone showed reduced cytokine responses to PHA compared to LPS.

Conclusions:

• Endogenous testosterone appears immunomodulatory, not immunosuppressive.
• Testosterone down-regulates potentially costlier immune activations (PHA-induced).
• Testosterone has less impact on less costly immune activations (LPS-induced), indicating immune investment trade-offs.