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 beta1 (TGFbeta1), and prostaglandin E2 (PGE2) 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 PGE2, IL-4, IL-10, and TGFbeta1. MATERIAL AND METHODS: New Zealand rabbits were injected with 50 microg/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 PGE2, IL-4, IL-10, and TGFbeta1 were measured with enzyme immunoassays. MEASUREMENTS AND MAIN RESULTS: Serum TSF activity, and levels of PGE2, IL-4, IL-10, and TGFbeta1 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. TGFbeta1 probably remained in the retentate after ultrafiltration, while PGE2 eluted at a higher retention time. The known anti-inflammatory factors TGFbeta1, IL-10, IL-4, and PGE2 only accounted for 13% of the total serum TSF activity of 614 U/mL. CONCLUSIONS: Lipopolysaccharide shock results in the release of multiple T-cell suppressive factors in addition to known immunosuppressive factors, all of which contribute to the anti-inflammatory response.
OBJECTIVES: Endotoxin induced suppression of cellular immune function is thought to contribute to septic complications in traumapatients. 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 beta1 (TGFbeta1), and prostaglandin E2 (PGE2) 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 PGE2, IL-4, IL-10, and TGFbeta1. MATERIAL AND METHODS:New Zealand rabbits were injected with 50 microg/kg of purified Escherichia colilipopolysaccharide. 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 PGE2, IL-4, IL-10, and TGFbeta1 were measured with enzyme immunoassays. MEASUREMENTS AND MAIN RESULTS: Serum TSF activity, and levels of PGE2, IL-4, IL-10, and TGFbeta1 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. TGFbeta1 probably remained in the retentate after ultrafiltration, while PGE2 eluted at a higher retention time. The known anti-inflammatory factors TGFbeta1, IL-10, IL-4, and PGE2 only accounted for 13% of the total serum TSF activity of 614 U/mL. CONCLUSIONS:Lipopolysaccharide shock results in the release of multiple T-cell suppressive factors in addition to known immunosuppressive factors, all of which contribute to the anti-inflammatory response.
Authors: Jane C Deng; Genhong Cheng; Michael W Newstead; Xianying Zeng; Koichi Kobayashi; Richard A Flavell; Theodore J Standiford Journal: J Clin Invest Date: 2006-08-17 Impact factor: 14.808
Authors: Juliana Reis Machado; Danilo Figueiredo Soave; Marcos Vinícius da Silva; Liliana Borges de Menezes; Renata Margarida Etchebehere; Maria Luiza Gonçalves dos Reis Monteiro; Marlene Antônia dos Reis; Rosana Rosa Miranda Corrêa; Mara Rúbia Nunes Celes Journal: Mediators Inflamm Date: 2014-12-30 Impact factor: 4.711