Objective: Arginine vasopressin (AVP; anti-diuretic hormone) and corticotropin-releasing hormone are the two major secretagogues of hypophyseal adrenocorticotropin (ACTH). Interleukin-6 (IL-6) is a potent stimulator of the human hypothalamic-pituitary-adrenal axis (HPA) and a secretagogue of both parvocellular and magnocelullar AVP. We have previously suggested that IL-6-stimulated AVP secretion may be the origin of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in inflammatory conditions.
Study design: To further elucidate the relationship between IL-6 and SIADH as well as IL-6 and HPA axis activity, we studied eight previously healthy children (age 6.3 +/- 4.8 [mean +/- SD] years, weight 23.8 +/- 10.5 kg) who--after sustaining head trauma--presented SIADH during hospitalization (for 7.1 +/- 3.8 days) in the pediatric intensive care unit (P-ICU). Routine blood samples were taken twice daily at 08:00 and 20:00 hours. All children but one survived. Measurements included blood and urine osmolality (BlOsm and UrOsm, respectively), serum cortisol (F) and IL-6, plasma ACTH and AVP. Correlations were assessed with linear regression among the areas under the curve (AUC) of BlOsm, UrOsm, ACTH, F, IL-6 and AVP, separately for BlOsm values <280 mOsm (SIADH phase) and > or = 280 mOsm (non-SIADH phase).
Results: During the SIADH phase AVP-AUC correlated positively with IL-6-AUC (r = +0.96, p<0.05), BlOsm-AUC correlated positively with AVP-AUC and F-AUC (r = +0.95 and +0.98, p<0.05, respectively) and F-AUC correlated positively with ACTH-AUC (r = +0.99, p<0.05). During the non-SIADH phase ACTH-AUC correlated positively with BlOsm-AUC (r = +0.96, p<0.05).
Conclusion: IL-6 secreted during an aseptic inflammatory state, such as sustaining head trauma with SIADH, is quantitatively correlated to AVP, indicating that this cytokine is directly and/or indirectly involved in the pathogenesis of SIADH.