Impairment of the Correlation between Urinary Contents of Alpha-1-Microglobulin and Ulinastatin Is Induced by Intracerebroventricularly Administered Interleukin-6 in Mice

We have found previously that the correlation between urinary contents of alpha-1-microglobulin (alpha1M) and ulinastatin (UT) depends on the type of neuropsychiatric disease. Since interleukin (IL)-1beta and IL-6 are closely involved in pathophysiological aspects of various neuropsychiatric diseases, effects of intracerebroventricularly (i.c.v.) administered IL-1beta and IL-6 on the correlation between urinary contents of these two glycoproteins were examined in mice, a species in which alpha1M and UT and also the correlation between the urinary contents thereof are expressed similarly to humans. Indices (volume, contents of creatinine, alpha1M and UT, and alpha1M/UT ratio) in urine collected after i.c.v. administrations of 2 and 20 ng of either IL-1beta or IL-6 were not statistically different from those of the vehicle-treated (control) groups. Neither IL-1beta (2 and 20 ng) nor the lower dose of IL-6 (2 ng) affected the positive correlation between urinary contents of alpha1M and UT. However, a higher dose of IL-6 (20 ng) nullified the positive correlation for 2 days after administration. Recovery to a positive correlation was thereafter displayed. These findings suggest that central IL-6 plays an important role in correlating urinary contents of alpha1M and UT without affecting the renal functions.