Avoidance of endotoxin-induced inflammation during studies of albumin clearance from caprine joints

Intra-articular injection of radiolabelled, commercial goat serum albumin (GSA) produces acute arthritis in caprine joints. This inflammation distorts clearance values and vitiates studies of normal lymphatic function. Endotoxin, routinely found in commercial albumin preparations, appears to cause this local reaction. We describe a simple method for the preparation of low-endotoxin, radioiodinated serum albumin from aseptically collected serum. We have used this technique to prepare GSA for use as a tracer molecule in clearance studies of synovial joint lymphatic function. The isolated protein exhibits antigenic and chemical characteristics indistinguishable from those of commercial GSA but contains at least 1000-fold less endotoxin. In contrast to commercial GSA preparations, this albumin does not produce local inflammation when injected into synovial joints and is cleared from caprine joints in the normal monoexponential manner. Low levels of endotoxin seriously distort studies of articular albumin kinetics and may induce comparable artifacts when commercial protein preparations are used to study other physiological systems.