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 (10³ 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.

Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF‐κB‐independent mechanism

“…It appears that in this model treatment with resveratrol impacts on prostanoid production in the lung; this result agrees with similar in vitro results described by Dallal and colleagues (44). Although studies have been published showing resveratrol to inhibit COX-1 and COX-2 gene expression in vitro (18,19), the results of this experiment suggest that the reduction in PGE 2 levels was not due to an impact on gene expression of either of these enzymes involved in the production in prostanoids.…”

Lipopolysaccharide desensitizes monocytes–macrophages to CD40 ligand stimulation

“…Several studies of the effects of non‐selective COX inhibition during sepsis have been conducted with the intent of determining whether COX inhibition is beneficial and safe. Available data indicate that COX inhibitors are generally safe and may ameliorate several clinical and immunological parameters 46,48–50 . However, treatment with COX inhibitors did not appear to improve the rate of survival in patients with sepsis even though it has been shown to ameliorate the extent of IL‐12 reduction and to provide survival advantage in septic animals 45,51 , 52 …”

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“…It is noteworthy that NS-398 exhibited protective effects in two models of sepsis characterized by infection in the setting of trauma-induced immunosuppression, whereas the drug was largely ineffective when sepsis was induced in immunocompetent animals. Dallal and coworkers [30] demonstrated that T-cell suppression during neonatal sepsis is accompanied by a decrease in IL-2 production. Such suppression was ameliorated by COX-2 inhibitor, suggesting a role for PGE 2 in suppressed T-cell-mediated immune function in neonatal sepsis.…”