IMMUNOSUPPRESSION AFTER ENDOTOXIN-SHOCK - THE RESULT OF MULTIPLE ANTIINFLAMMATORY 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 prostag landin E(2) (PGE(2)) in addition to other factors, in inducing immunos uppression, Design: T-cell suppressive factors (TSF) in serum ultrafil trates were separated and tested for the presence of the known suppres sive factors PGE(2), IL-4, IL-10, and TGF beta(1). Material and Method s: New Zealand rabbits were injected with 50 mu g/kg of purified Esche richia coil lipopolysaccharide, Animals were exsanguinated after 48 ho urs and serum was separated by ultrafiltration (cutoff 50 kd), TSK HW- 40 size exclusion chromatography, and Q-Sepharose anion exchange chrom atography. TSF activities of chromatographic fractions and serum sampl es 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 w ith enzyme immunoassays. Measurements and Main Results: Serum TSF acti vity, and levels of PGE(2), IL-4, IL-10, and TGF beta(1) were increase d after endotoxemia, Size exclusion chromatography revealed three majo r fractions (TSF1-3) with up to 600 times more TSF activity compared w ith controls, IL-4 and IL-10 were found in TSF1 and TSF3. Further sepa ration of TSF1 by anion exchange chromatography revealed a total of ei ght different T-cell suppressive factors, TGF beta(1) probably remaine d in the retentate after ultrafiltration, while PGE(2) eluted at a hig her retention time, The known anti-inflammatory factors TGF beta(1), I L-10, IL-4, and PGE(2) only accounted for 13% of the total serum TSF a ctivity of 614 U/mL, Conclusions: Lipopolysacchoride shock results in the release of multiple T-cell suppressive factors in addition to know n immunosuppressive factors, all of which contribute to the antiinflam matory response.