title: T-cell proliferative responses following sepsis in neonatal rats.
abstract: Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment of animals with COX-2 inhibitor also significantly prevented the sepsis-associated mortality in neonates. In conclusion, the present study demonstrated T-cell suppression during neonatal sepsis is accompanied by a decrease in IL-2 production. Such suppressions were ameliorated with COX-2 inhibitor suggesting a role for PGE2 in the suppressed T-cell-mediated immune function in neonatal sepsis.
authors.affiliation: Department of Surgery, Trauma/Critical Care Research Labs, Strich School of Medicine, Ronald McDonald Children's Hospital, Loyola University Medical Center, Maywood, Ill 60153, USA.
authors.forename: Ousama
authors.initials: O
authors.lastname: Dallal
authors.forename: Thyyar M
authors.initials: TM
authors.lastname: Ravindranath
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Annamarie
authors.initials: A
authors.lastname: Kohn
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Muraskas
authors.forename: Shahla Y
authors.initials: SY
authors.lastname: Namak
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Alattar
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Sayeed
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001442:Bacteroides Infections / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D001441:Bacteroides fragilis; D001786:Blood Glucose / Q000032:analysis; D002455:Cell Division; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004927:Escherichia coli Infections / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*
chemical_list: D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D007376:Interleukin-2; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D019344:Lactic Acid; D015232:Dinoprostone