Steensberg · American journal of physiology. Endocrinology and metabolism 2003 · Controlled human infusion trial · n=?

IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans.

Cited 1131 times in the scientific literature.

Level 3 - non-randomized controlled study

Controlled human experimental study; randomization and blinding are not reported in the abstract.

PubMed 12857678 · doi:10.1152/ajpendo.00074.2003 · record verified 2026-08-27

What was done

Young healthy volunteers received a 3-hour low-dose intravenous infusion of recombinant human interleukin-6 (rhIL-6, achieving plasma levels of ~140 pg/ml, corresponding to strenuous exercise) or saline. Researchers measured circulating levels of TNF-alpha, IL-1 receptor antagonist (IL-1ra), IL-10, C-reactive protein (CRP), cortisol, epinephrine, leukocyte counts (neutrophils and lymphocytes), body temperature, mean arterial pressure, and heart rate.

What was found

Infusion of rhIL-6 achieved plasma levels of ~140 pg/ml and did not increase pro-inflammatory TNF-alpha. Compared with saline, rhIL-6 elevated anti-inflammatory cytokines IL-1ra and IL-10, and increased CRP at 3 hours post-infusion with further elevation at 16 hours. rhIL-6 also increased plasma cortisol, circulating neutrophils, and decreased lymphocyte counts, without affecting plasma epinephrine, body temperature, mean arterial pressure, or heart rate. Numerical values for cytokine and cell changes were not provided in the abstract.

Why it matters

It demonstrates that transient physiological elevations of IL-6 provoke anti-inflammatory cytokine release (IL-1ra, IL-10) and cortisol-mediated leukocyte redistribution rather than a pro-inflammatory cascade, elucidating the mechanism behind exercise-induced immune shifts.

Limits

The abstract does not disclose the sample size, sex distribution, or whether the infusion was randomized or blinded. Effects of chronic IL-6 exposure and applicability to clinical or older populations were not studied.

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