[Clinical trial to verify the value of the CD14(+) monocyte human leukocyte antigen DR as a marker in evaluating immunosuppression in patients with severe sepsis].

Objective: To verify that CD14(+) monocyte human leukocyte antigen DR (HLA-DR) may serve as a reliable index for immunosupression, and for prediction of prognosis as well as to evaluate the efficacy of Thymopentin (TP-5) to enhance immunologic function in patients with severe sepsis, and to evaluate the validity of compensatory anti-inflammatory response syndrome (CARS).

Methods: Patients in a SICU with symptoms and signs of severe sepsis conforming to the criteria set forth by ACCP/SCCM were enrolled in this clinical trial. CD14(+) monocyte HLA-DR was determined by flow cytometry. To those with HLA-DR<30%, TP-5, 1 mg, q.d. was administered till HLA-DR raised or death occurred. Before the treatment was begun and ended, CD14(+) monocyte HLA-DR(+) and cytokines[tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, IL-13] were respectively measured.

Results: Totally, 20 patients were enrolled in this study. Among them 15 survived and 5 died. After treatment with TP-5, CD14(+) monocyte HLA-DR was elevated in almost all the patients, including the nonsurvivors. However, only a statistically significant difference between the initial values and the final values was noted in the survivors. The levels of TNF-alpha and IL-6 dropped significantly concomitantly with the elevation of the CD14(+) monocyte HLA-DR in survivors. On the contrary, in the patients who died there was a tendency of an elevation of levels of these cytokines. No significant difference was found between the initial and final levels of both IL-10 and IL-13 with the treatment.

Conclusion: 1. It was reconfirmed that the CD14(+) monocyte HLA-DR could be a reliable and valuable index to judge immunosupression in septic patients and determine the effectiveness of immunostimulative therapy. 2. It was reconfirmed that the level of CD14(+) monocyte HLA-DR can serve as an index to predict the outcome of septic patients. 3. TP-5, as a new immunostimulative agent used in sepsis, might be effective to revert immunosupression. However, a further clinical trial with a larger number of patients and a better control should be done to finally verify it. 4. It is found that immunosupression do not seem to be related with the balance between pro- and anti-inflammatory cytokines, suggesting that the hypothesis of CARS should be further appraised.