STUDY: Production of cytokines to blame

JOURNAL: Am J Respir Crit Care Med 2002;166:1055-1061

AUTHORS: Dr. E. Rand Sutherland

ABSTRACT: The production of cytokines after melatonin stimulation by mononuclear cells from patients with asthma suggests that melatonin may exacerbate their symptoms, according to a report in the American Journal of Respiratory and Critical Care Medicine.

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COMMENTARY: Patients with nocturnal asthma show circadian variations in airflow limitation, the authors explain, and melatonin is a key regulator of circadian rhythms as well as an important immunomodulatory in allergic diseases.

Dr. E. Rand Sutherland and colleagues from National Jewish Medical and Research Center and the University of Colorado Health Sciences Center in Denver, Colorado evaluated the effect of melatonin stimulation on peripheral blood mononuclear cell (PBMC) cytokine production at 4 a.m. and 4 p.m. in 5 normal control subjects, 6 patients with nocturnal asthma, and 12 patients with non-nocturnal asthma.

Melatonin stimulation significantly increased the production of IL-1, IL-6, and TNF-alpha by zymosan-stimulated PBMCs in all subject groups at both stimulation times, the authors report.

Nocturnal asthma patients had higher IL-1 production levels than normal subjects did, the report indicates, though (for both groups) 4 a.m. and 4 p.m. levels did not differ. Patients with non-nocturnal asthma had IL-1 production levels similar to controls subjects at 4 a.m., but these levels increased nearly 5-fold at 4 p.m.

Melatonin-stimulated IL-6 production patterns were very similar to those seen with IL-1 production, the results indicate.

In contrast, both nocturnal asthma patients and non-nocturnal asthma patients showed substantially higher melatonin-stimulated TNF-alpha production at 4 p.m. than at 4 a.m., the researchers note, whereas control subjects showed similar increases at both times.

These results suggest differential immunomodulatory effects of melatonin based on asthma clinical phenotype and may indicate an adverse effect of exogenous melatonin in asthma. For these patients, avoidance of melatonin may be appropriate until further information about the clinical effect of melatonin in asthma becomes available.