Immunosuppression after endotoxin shock: The result of multiple anti-inflammatory factors

Objectives: Endotoxin induced suppression of cellular immune function is thought to contribute to septic complications in trauma patients, A rabbit model of endotoxemia was used to determine the relative roles of the anti-inflammatory factors interleukin-4 (IL-4), interleukin-10 (IL-10), transforming growth factor beta(1) (TGF beta(1)), and prostaglandin E(2) (PGE(2)) in addition to other factors, in inducing immunosuppression, Design: T-cell suppressive factors (TSF) in serum ultrafiltrates were separated and tested for the presence of the known suppressive factors PGE(2), IL-4, IL-10, and TGF beta(1). Material and Methods: New Zealand rabbits were injected with 50 mu g/kg of purified Escherichia coli lipopolysaccharide, Animals were exsanguinated after 48 hours and serum was separated by ultrafiltration (cutoff 50 kd), TSK HW-40 size exclusion chromatography, and Q-Sepharose anion exchange chromatography. TSF activities of chromatographic fractions and serum samples were measured with a mitogen induced in vitro T-cell proliferation assay, Levels of PGE(2), IL-4, IL-10, and TGF beta(1), were measured with enzyme immunoassays. Measurements and Main Results: Serum TSF activity, and levels of PGE(2), IL-4, IL-10, and TGF beta(1) were increased after endotoxemia, Size exclusion chromatography revealed three major fractions (TSF1-3) with up to 600 times more TSF activity compared with controls, IL-4 and IL-10 were found in TSF1 and TSF3. Further separation of TSF1 by anion exchange chromatography revealed a total of eight different T-cell suppressive factors, TGF beta(1) probably remained in the retentate after ultrafiltration, while PGE(2) eluted at a higher retention time, The known anti-inflammatory factors TGF beta(1), IL-10, IL-4, and PGE(2) only accounted for 13% of the total serum TSF activity of 614 U/mL, Conclusions: Lipopolysacchoride shock results in the release of multiple T-cell suppressive factors in addition to known immunosuppressive factors, all of which contribute to the antiinflammatory response.