Immunomodulatory effects of melatonin in asthma

E. Rand Sutherland, Richard J. Martin, Misoo C. Ellison, Monica Kraft

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Patients with nocturnal asthma demonstrate circadian variations in airway inflammation. We hypothesized that melatonin, a circadian rhythm regulator, modulates circadian inflammatory variations in asthma. The effect of melatonin stimulation on peripheral blood mononuclear cell cytokine production was evaluated at 4:00 P.M. and 4:00 A.M. in normal control subjects, patients with nocturnal asthma, and patients with non-nocturnal asthma. Melatonin was proinflammatory, causing significantly increased production of interleukin-1, interleukin-6, and tumor necrosis factor-α at 4:00 P.M. and 4:00 A.M. in all subject groups (range, 12.8 ± 3.3 to 131.72 ± 16.4%, p ≤ 0.0003). The observed increases in cytokine production did not change between 4:00 P.M. and 4:00 A.M. in control subjects or in patients with nocturnal asthma (p > 0.05, both cases). At 4:00 P.M., the cytokine response to melatonin of patients with nocturnal asthma was greater than that of control subjects or patients with non-nocturnal asthma and did not change significantly at 4:00 A.M. At 4:00 P.M., the cytokine response of patients with non-nocturnal asthma was less than that of patients with nocturnal asthma and rose significantly at 4:00 A.M. (p = 0.0001, all comparisons). Melatonin is proinflammatory in both patients with asthma and healthy subjects. Patients with nocturnal asthma demonstrate the largest daytime cytokine response and cannot be further stimulated at 4:00 A.M., suggesting chronic overstimulation in vivo. These results suggest differential immunomodulatory effects of melatonin based on asthma clinical phenotype and may indicate an adverse effect of exogenous melatonin in asthma.

Original languageEnglish (US)
Pages (from-to)1055-1061
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Issue number8
StatePublished - Oct 15 2002


  • Hormones
  • Inflammation
  • Pathogenesis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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