Inappropriately normal plasma ACTH and cortisol concentrations in the face of increased circulating interleukin-6 concentration in exercise in patients with sarcoidosis

Sarcoidosis is an autoimmune disease, and hypothalamic-pituitary-adrenal (HPA) axis activity is blunted in autoimmunity. Exercise stimulates the HPA axis, and we hypothesized that in sarcoidosis patients responses to treadmill exercise would be reduced. Hence, we studied 44 sarcoidosis patients [27 untreated (age, mean ± SD, 42 ± 2 years, 12 males, 15 females) and 17 dexamethasone treated (age, 46 ± 4 years, 7 males, 10 females)] and 20 healthy controls (40 ± 5 years old, 9 males, 11 females). Blood samples were drawn before, at peak (exhaustion), and 15 min after treadmill exercise for adrenocorticotropic hormone (ACTH), cortisol, tumor necrosis factor (TNF), interleukin-1β (IL-1β) and IL-6 measurements. At peak, plasma ACTH (pg/ml) was increased in untreated (mean ± SE, ΔACTH = 162.8 ± 29.9) and treated (ΔACTH = 123.3 ± 48.1) patients and controls (ΔACTH = 112.3 ± 41.7). Post-exercise, cortisol (ng/ml) was increased (p < 0.05) in untreated patients (Δcortisol = 48.4 ± 14.7) and controls (Δcortisol = 46.0 ± 15.9), but not significantly in treated patients (Δcortisol = 1.43 ± 2.56). At baseline, serum IL-6 (pg/ml) and TNF (pg/ml) were higher in untreated (3.02 ± 0.54 and 3.89 ± 0.72) and treated (1.75 ± 0.33 and 2.16 ± 1.00) patients, respectively, than in controls (0.80 ± 0.66 and 1.58 ± 0.32). At peak exercise, IL-6 was increased in untreated (ΔIL-6 = 0.96 ± 0.14) and treated (ΔIL-6 = 0.91 ± 0.47) patients and controls (ΔIL-6 = 0.96 ± 0.18); IL-1β was increased only in controls. Hence, the HPA axis of untreated sarcoidosis patients and controls responded similarly to treadmill exercise. In sarcoidosis patients, increased IL-6 was associated with HPA stimulation. Cortisol concentrations were similar between patients and controls, although IL-6 concentrations were higher in patients. Thus, in the face of chronically elevated IL-6 levels in sarcoidosis, there may be dysfunctional IL-6-induced HPA responses or HPA adaptation to high IL-6 concentrations.