The calendar of cytokines: Seasonal variation of circulating cytokines in chronic venous insufficiency

Objectives: To assess if in chronic venous insufficiency, there is a seasonal variation of cytokines levels which could explain the typical worsening of symptoms during Spring and Summer. Participants: From 193 chronic venous insufficiency patients, we selected 32 patients in clinical stage C2-C3 of the Clinical-Etiology-Anatomy-Pathophysiology classification. Design: A prospective, comparative and blinded cytokines assessment in two different seasons. Setting: We sorted patients by two homogenous groups, 17 Autumn Group and 15 Spring Group. A complete clinical and haemodynamic assessment and laboratory analysis of 22 circulating cytokines were performed on each patient. Main outcome measures: Circulating cytokines levels assessment. Results: The two groups resulted homogenous for age, gender, clinical class, and haemodynamic parameters. Comparing cytokines expressions in Autumn Group vs. Spring Group, we found a significant difference of 11 out of 22 circulating cytokines (p < 0.05). Particularly Eotaxin, Interleukin-8, Monocyte Chemoattractant Protein-1, Tumour Necrosis Factor-alpha and Vascular Endothelial Growth Factor were increased in Autumn compared to the Control Group (p < 0.001); while significantly reduced in Spring, within the normal range (p, not significant). Conclusions: Symptoms of chronic venous insufficiency are self-reported by patients more intense during warm seasons. Surprisingly, in our study, cytokines levels were significantly higher during Autumn and downregulated in Spring. These variations show for the first time the presence of a 'Calendar of Cytokines' in chronic venous insufficiency, which needs to be further investigated.