Impact of Immunonutrition on T Cell Activation: A Randomized Control Study in Cardiac Surgery Patients

Abstract

Background. Cardiac surgery provokes an intense inflammatory response that can cause an immuno-suppressive state and adverse postoperative outcomes. We recently showed that postoperative immunonutrition with glutamine in “fragile” low-risk cardiac surgery patients was associated with a significantly increased level of CD3+ and CD4+ T cells. In order to clarify the biological relevance and clinical importance of these findings, we investigated whether an increase in the CD4+ T cell level was caused by changes in the systemic inflammatory response (caused by surgery or infection) and if it was associated with their activation status. Methods. A randomized control study of low operative risk but “fragile” cardiac surgery patients was per-formed. Patients were randomized into immunonutrition (IN) and control groups (C). The IN group received normal daily meals plus special immune nutrients for 5 days postoperatively, while the C group received only normal daily meals. Laboratory parameters were investigated before surgery and on the sixth postoperative day and the groups were compared accordingly. The expression of the CD69+ marker was investigated to deter-mine T cell activation status. Serum concentrations of cytokines (interleukin-10 (IL-10), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6)) and C-reactive protein (CRP) were determined to assess the systemic inflammatory response, while procalcitonin (PCT) levels were evaluated to confirm or deny possible bacterial infection. Results. Fifty-five patients were enrolled in the study. Twenty-seven (49.1%) were randomized in the IN group. Results show that on the sixth postoperative day, the CD4+CD69+ and CD8+CD69+ counts did not differ between the IN and C groups, accordingly 0.25 [0.16–0.50] vs 0.22 [0.13-0.41], p=0.578 and 0.13 [0.06– 0.3] vs 0.09 [0.05–0.14], p=0.178. Also, statistically significant differences were not observed in the cytokine levels (IN and C groups: TNF-α 8.13 [7.32–10.31] vs 8.78 [7.65–11.2], p=0.300; IL-6 14.65 [9.28–18.95] vs 12.25 [8.55–22.50], p=0.786; IL-10 5.0 [5.0–5.0] vs 5.0 [5.0–5.0], p=0.343 respectively), which imply that an elevated T cell count is not associated with the systemic inflammatory response. Also, PCT (IN and C groups: 0.03 [0.01–0.09] vs 0.05 [0.03–0.08], p=0.352) and CRP (IN and C groups 62.7 [34.2–106.0] vs 63.7 [32.9–91.0], p=0.840) levels did not differ between the two groups. Moreover, low levels of PCT indicated that the increase in T cell count was not determined by bacterial infection. Conclusions. Our findings showed that CD4+ T cell levels were associated with neither the systemic inflammatory response nor bacterial infection. Secondly, increases in T cells are not accompanied by their activation status. These results suggest a hypothesis that a higher postoperative T cell concentration may be associated with postoperative immunonutrition in low-risk cardiac surgery patients with intact cellular vital-ity, i.e. “fragile”. However, immunonutrition alone did not affect T cell activation status.