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    Objective To observe the seasonal changes in serum levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and melatonin (MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis.
    Methods One hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer (n=80) and winter (n=80) respectively:normal group, collagen-induced arthritis (CIA) model group, operation group, and sham-operation group (n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was.The serum levels of IL-1β, IL-6 and MT in different groups were measured by radioimmunoassay.
    Results Compared with the normal group, the serum levels of IL-1βand IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter (IL-1βin summer, P=0.008, P<0.01, P=0.012; IL-1β in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024;IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1βand IL-6 in winter were higher than in summer, but with no statistically significant differences (P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group (P=0.002, 0.008) and the sham-operation group (P=0.003, 0.007), while significantly decreased in the operation group (P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter (P=0.947).
    Conclusions The increase of serum levels of IL-1β and IL-6 may exacerbate the inflammatory reaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1β, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.

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