HUMAN-IGG PRODUCTION IN-VIVO - DETERMINATION OF SYNTHETIC RATE BY NONRADIOACTIVE TRACER INCORPORATION

Exposure of Ab-secreting cells to selected hormones, cytokines, and dr ugs alters the rate of Ig production in vitro. Whether these effects a re important clinically is unknown because there are no safe, reproduc ible, and appropriate techniques for measuring Ig synthesis in vivo. W e developed a stable isotope tracer method to measure IgG secretion in to plasma. L-[1-C-13]Leucine was given as a priming dose followed by a constant i.v. infusion over 8 h. Tracer accrual in IgG, determined by mass spectrometry, was linear from 2 to 8 h of the infusion. The norm al rate of IgG synthesis into plasma assessed in 21 healthy subjects w as 860 +/- 310 mg/day (mean +/- SD). The synthetic rate measurements w ere remarkably reproducible (coefficient of variation = 10.5%). Simult aneous analysis of leucine kinetics allows, for the first time, Ig sec retion to be studied in the context of whole body protein economy. IgG secretion into plasma accounts for 0.3% of whole body protein synthes is. Experimental support for a key metabolic assumption, that tracer e nrichment in plasma and that at the site of Ige synthesis were similar , came from a comparison of synthetic rates derived from low dose and high dose tracer infusions. Measurement of Ig secretion by tracer inco rporation is rapid and reproducible. In contrast to older methods that rely on radioisotope disappearance, the tracer incorporation method i s safe for serial measurements in an individual and will be useful for quantitative studies of treatment effects and immune regulation in vi vo.