The Severity of Infection Induces a Shift in the Type 1/Type 2 T-Helper Cell Balance in Patients with or without Peritonitis

Abstract

Background

: A type-1 to type-2 T-helper cell (Th1/Th2) shift is hypothesized to occur among patients with severe trauma and pancreatitis. It was hypothesized that the Th2 situation caused an immune-suppressed period that led to a critical imbalance in the patients' conditions, with an increased risk of multiple organ failure and mortality.

Methods

: In eight patients with localized intra-abdominal infection (diverticulitis) and six patients with peritonitis due to perforation of a hollow viscus, we examined the cytokine response of CD3⁺ T cells in the greater omentum and in the peripheral blood by in vitro stimulation, intracellular cytokine staining, and flow cytometry for TNF-α, IFN-γ, IL-2, and IL-4. Follow-up cytokine assays were carried out on peripheral blood on days 3 and 7. Different levels of cytokine expression in each group were examined to determine the origin of the lymphocytes, both from omentum or peripheral blood. Cytokine production in the diverticulitis group was compared with that of the peritonitis patients.

Results

: In localized infections (diverticulitis), there was higher expression of TNF-α (51%/35% positive cells in omentum/blood), IFN-γ (47%/32%), and IL-2 (33%/20%) in the omentum than in the peripheral blood mononuclear cells (PMBCs), but this was not true for IL-4 expression (0.8%/1.3%). In patients with peritonitis, there were no differences in cytokine expression between lymphocytes from the greater omentum and from PMBCs for TNF-α (18%/21% omentum/blood), IFN-γ (20%/22%), IL-2 (16%/12%), or IL-4 (10.9%/7.6%). Compared to the diverticulitis group, patients with peritonitis showed reduced expression for TNF-α, IFN-γ, and IL-2, but there was a significantly higher response for IL-4 for both compartments.

Conclusions

: There was a shift from Th1 to Th2 in patients with severe clinical symptoms of peritonitis. Immune suppression is evident because of the T cell response in the greater omentum, but immunosuppression seems to not reach its maximum level before day 7 post operation. This differs from findings in multiple trauma and pancreatitis; however, it is parallel to the clinical situation in patients with peritonitis.