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 (alpha 1M) and ulinastatin (UT) depends on the type of neuropsychiatric disease. Since interleukin (IL)-1 beta and IL-6 are closely involved in pathophysiological aspects of various neuropsychiatric diseases, effects of intracerebroventricularly (i.c.v.) administered IL-1 beta and IL-6 on the correlation between urinary contents of these two glycoproteins were examined in mice, a species in which alpha 1M and UT and also the correlation between the urinary contents thereof are expressed similarly to humans. Indices (volume, contents of creatinine, alpha 1M and UT, and alpha 1M/UT ratio) in urine collected after i.c.v. administrations of 2 and 20 ng of either IL-1 beta or IL-6 were not statistically different from those of the vehicle-treated (control) groups. Neither IL-1 beta (2 and 20 ng) nor the lower dose of IL-6 (2 ng) affected the positive correlation between urinary contents of alpha 1M and CIT. 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 alpha 1M and UT without affecting the renal functions.