Circadian distribution of serum cytokines in multiple sclerosis

The purpose of this study was to examine circadian distribution of selected cytokine levels (IL-2, IL-10, GM-CSF, TNF-alpha, and IFN-gamma) in serum of subjects with active Multiple Sclerosis (MS) and non-MS subjects.

Six females (36-56y) and five males (52-68y) with active MS volunteered and consented for the study conducted at Special Diagnostic Ward of this hospital. All subjects gave their medical history and were given complete physical examination. Low purine meals were served at 16:30, 07:30 and 13:00 h. Lights were "OFF' at 22:30 hr and "ON" at 06:30h. Blood collections were made at 3h intervals over a 24h period of time. Six healthy male subjects (53-76y) subjects' data were obtained from a study conducted 3 years previously using the same procedural protocol. Cytokine assays were assessed using commercial enzyme-linked immuno-absorbent procedure. Time series of average data and the range of change between the highest and lowest concentrations are presented for MS subjects along with data from non-MS subjects.

IL-2, IL-10, and GM-CSF levels were significantly reduced in females with MS when compared with levels of healthy subjects while their IL-6 levels were increased. The IL-6, GM-CSF and TNF-alpha levels in males with MS were below detection limits. The TNF-alpha levels were essentially similar in MS females and healthy subjects.

These preliminary studies, although with very small number of patients and healthy male controls appear to suggest that the circadian analysis of cytokines and other markers of immunity may have utility in understanding the pathogenesis of diseases like MS.