Published ahead of print on August 8, 2002, doi:10.1164/rccm.200204-356OC
© 2002 American Thoracic Society
Immunomodulatory Effects of Melatonin in AsthmaDepartment of Medicine, National Jewish Medical and Research Center; and University of Colorado Health Sciences Center, Denver, Colorado Correspondence and requests for reprints should be addressed to E. Rand Sutherland, M.D., 1400 Jackson Street, B-123, Denver, CO 80206. E-mail: sutherlande{at}njc.org ABSTRACT
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-
Key Words: hormones • inflammation • pathogenesis This article has been cited by other articles:
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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. 
