The origin and turnover rates of cerebrospinal fluid albumin and gamma-globulin in man

The extent of equilibration of intravenously-injected [¹²⁵I]immunoglobulin-G (IgG) between serum and cerebrospinal fluid (CSF) was studied in patients with normal and selectively-elevated concentrations of IgG in CSF. CSF IgG appeared to be derived from serum IgG in those patients with normal lumbar fluid IgG concentration, while 37-88% of the CSF IgG was derived from an extravascular pool, presumably within the nervous system, in the patients with selectively-elevated IgG concentrations. The rate of flux of albumin and IgG into the entire CSF compartment was estimated during ventriculo-lumbar perfusion. Albumin influx was comparable in the control and elevated CSF IgG groups (0.086 mg/min and 0.100 mg/min, respectively). IgG influx was increased 6-fold in the elevated IgG group as compared with the control group (0.107 mg/min and 0.018 mg/min, respectively). The increased rate of influx of IgG was felt to represent the contribution to CSF of a pool of γ-globulin synthesized within the nervous system. The CSF pool size of albumin and IgG was estimated in 7 patients, from which values the fractional turnover rates of CSF albumin and IgG were calculated. The turnover rate constants for albumin (0.0035 min^-1) and IgG (0.0036 min^-1) agreed well with the turnover rate constant for net formation of CSF (0.0034 min^-1), supporting the concept that proteins are removed from CSF during reabsorption of fluid in bulk.