Interleukin 6 and cortisol levels changes during cardiopulmonary exercise test in patients with sarcoidosis

OBJECTIVE: Current evidence suggests that autoimmune phenomena are involved in the pathogenesis of sarcoidosis, a chronic multisystem, granulomatous disease. A defective hypothalamic-pituitary-adrenal (HPA) axis characterizes autoimmune diseases. Exogenously administered and endogenous exercise-induced interleukin (IL) 6 are known to stimulate the HPA axis. To examine the HPA axis responsiveness in patients with sarcoidosis, we measured IL-6 and cortisol levels under basal conditions and during exercise. METHOD: We submitted 26 untreated patients with sarcoidosis, 9 patients treated with corticosteroids and 10 normal controls to maximal cardiopulmonary exercise testing. We measured IL-6 and cortisol levels in blood samples drawn before, at peak exercise and 15 min after exercise. IL-6 was measured by a specific ELISA and cortisol by a RIA. RESULTS: Interleukin 6 levels at baseline were significantly higher (P < 0.05) in untreated patients (mean±SD 3.12±2.93 pg/mL) and in patients receiving corticosteroids (3.2±5.96 pg/mL) than in controls (1.03±0.80 pg/mL). Cortisol levels at baseline were comparable in all groups (111.54+↑8.38, 105.57±71.43 and 106.00±35.20 ng/mL, respectively). Interleukin 6 levels were significantly increased (P < 0.05) at peak and 15 min after exercise in untreated patients (4.02±3.05 and 4.46±4.41 pg/mL, respectively) and controls (1.79±1.24 and 1.60±1.16 pg/mL, respectively). Similarly, cortisol levels were significantly increased (P<0.05) at peak and 15 min after exercise both in untreated patients (162.60±91.40 and 157.74±61.80 ng/mL, respectively) and controls (133.22±72.22 and 152.00±36.97 ng/mL, respectively). Cortisol and IL-6 levels did not increase during exercise in patients receiving corticosteroids. CONCLUSIONS: We conclude that in sarcoidosis the HPA axis is hyporesponsive to the chronically increased levels of endogenous IL-6, although it can still be activated by exercise. This might indicate a direct and/or indirect involvement of a defective HPA axis in the pathogenesis of sarcoidosis. Alternatively, it might indicate a resetting of the HPA axis to the chronically elevated levels of IL-6.