Circadian rhythm and the influence of physical activity on circulating surfactant protein D in early and long-standing rheumatoid arthritis

Abstract

Surfactant protein D (SP-D) belongs to the collectin family and has pro-and anti-inflammatory capacities depending on its oligomerization. Previously, circulating SP-D was shown to be decreased in early rheumatoid arthritis (RA) and negatively correlated to disease activity. This study aimed at assessing the diurnal rhythmicity and the influence of physical activity on circulating SP-D in patients with RA at different stages compared with healthy individuals. Patients with early RA (ERA) with disease duration <6 months and with long-standing RA (LRA) with disease duration 5-15 years were included in two sub-studies. Healthy individuals served as controls. Diurnal variation: blood samples were collected every 3 h from 7 a.m to 10 p.m and the following morning. Physical activity: blood sampling was done before and after standardized physical challenge. SP-D was measured by ELISA. SP-D exhibited diurnal variation in healthy controls (n = 15) and in patients with ERA (n = 9) and LRA (n = 9) with peak values at 10 a.m. and nadir in the evening (controls: P < 0.001, ERA: P = 0.004 and LRA: P = 0.009). Three hours after cessation of physical activity, SP-D decreased below pre-exercise levels in both ERA (n = 10), LRA (n = 10) and controls (n = 13) (ERA: P < 0.001, LRA: P < 0.001 and controls: P = 0.005). In patients with RA, the decline was already observed 1 h post-exercise. Circulating SP-D exhibits diurnal variation both in patients with RA at different stages and in healthy controls. SP-D in serum decreases following physical activity in health and RA disease. This study underscores the need of standardized blood sampling conditions in future studies on SP-D.