Carrillo-Vico · FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2004 · In vitro cell culture experiment · n=?

Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance.

Cited 460 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

In vitro bench study using human cell cultures

PubMed 14715696 · doi:10.1096/fj.03-0694fje · record verified 2026-08-30

What was done

Researchers evaluated whether resting and phytohemagglutinin-stimulated human lymphocytes synthesize and secrete melatonin in vitro. They examined the presence of enzymatic synthesis machinery, measured melatonin levels released into the culture medium, applied pharmacological inhibitors of biosynthetic enzymes and protein synthesis, and assessed the impact of these interventions (plus exogenous melatonin rescue) on interleukin-2 (IL-2) production.

What was found

Both resting and stimulated human lymphocytes synthesized and released melatonin, reaching culture medium concentrations up to five times nocturnal physiological serum levels. Inhibiting melatonin biosynthetic enzymes or protein synthesis significantly decreased melatonin release and reduced IL-2 production. Supplementation with exogenous melatonin restored IL-2 production. Specific quantitative baseline values, donor numbers, and statistical confidence intervals were not reported in the abstract.

Why it matters

This study identifies human lymphocytes as an extrapineal source of melatonin, providing evidence that endogenous melatonin can act locally as an intracrine, autocrine, or paracrine regulator of immune signaling and cytokine production.

Limits

This was strictly an in vitro bench investigation; in vivo physiological dynamics were not measured. The abstract does not disclose donor sample size, donor clinical characteristics, exact quantitative concentrations, or statistical effect sizes.

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