Immunoglobulin Levels and Lymphocyte Subsets Following Cardiac Operations: Further Evidence for a T-Helper Cell Shifting[*]

Abstract

Background: Recent data indicate that cardiac surgery with cardiopulmonary bypass (CPB) results in an imbalance of T-helper cell subsets towards the anti-inflammatory pathway mediating humoral immune response. However, little is known about immunoglobulin levels as an important part of humoral immune response after CPB. Therefore, the objectives of this study were 1) to elucidate the effects of CPB on perioperative immunoglobulin levels, and 2) to find out if alterations in lymphocyte subsets are related to these findings. Methods: Blood samples from 83 patients undergoing elective cardiac operation were taken preoperatively (d0), on the first (d1), third (d3), and fifth day (d5) after operation. Levels of immunoglobulin (Ig) E, IgM, and IgG, including the subclasses IgG 1 - 4, were measured. IgG2/IgE-ratio was used as indicator for TH1/TH2 shifting, and production of tetanus antibodies (AB) was investigated as an in vivo parameter of humoral immune reaction. The number and percentage of T- and B-lymphocyte subsets were assessed in a subgroup of 50 patients to answer the second question. Results: Clinically, no mortality or major morbidity were observed. IgE levels did not change until d3 and increased significantly on d5. In contrast, both IgG and IgM levels decreased significantly on d1. While IgM returned to baseline (BL) on d5, IgG levels remained below BL until d5. IgG2/IgE-ratio decreased significantly on d1, reached its nadir on d3 and remained depressed until d5. The number of T-lymphocytes decreased on d1 as well as the number of B-cells. T-cells returned to BL on d5, B-cells on d3. However, while the percentage of T-cells decreased on d1, the percentage of B-cells increased. The percentage of T-cells returned to BL on d3, and B-cell percentage returned to BL on d5. Tetanus AB production did not change until d5 when it increased significantly. Conclusions: 1) Increase of IgE and tetanus AB production indicate that humoral immune response is not affected by CPB, but possibly even enhanced. The relative increase of B-cells is in line with this hypothesis. 2) Postoperative changes in immunoglobulin levels provide further evidence for a TH1/TH2-shifting. 3) The transient deficit in IgM-and IgG levels did not result in clinically adverse events. Thus, therapeutic intervention appears not to be required.

Immunoglobulin levels - TH1/TH2-shifting - cardiac surgery

References

• 1 Markewitz A, Faist E, Weinhold C. et al . Alterations of cell-mediated immune response following cardiac surgery.  Eur J Cardiothorac Surg. 1993;  7 193-199
• 2 Markewitz A, Lante W, Franke A, Marohl K, Kuhlmann W D, Weinhold C. Alterations of cell-mediated immunity following cardiac operations: Clinical implications and open questions.  Shock. 2001;  16 10-15
• 3 Franke A, Lante W, Fackledey V, Becker H P, Thode C, Kuhlmann W D, Markewitz A. Proinflammatory and antiinflammatory cytokines after cardiac operation: Different cellular sources at different times.  Ann Thorac Surg. 2002;  74 363-371
• 4 Mayumi H, Zhang Q W, Nakashima A. et al . Synergistic immunosuppression caused by high-dose methylprednisolone and cardiopulmonary bypass.  Ann Thorac Surg. 1997;  63 129-137
• 5 Markewitz A, Faist E, Lang S, Hültner L, Weinhold C, Reichart B. An imbalance in T-helper cell subsets alters immune response after cardiac surgery.  Eur J Cardiothorac Surg. 1996;  10 61-67
• 6 Sablotzki A, Dehne M G, Mann V. et al . Plasma levels of selectins and interleukins in cardiovascular surgery using cardiopulmonary bypass.  Thorac Cardiovasc Surg. 1999;  47 26-31
• 7 Mosman T, Moore K W. The role of IL-10 in crossregulation of TH1 and TH2 responses.  Immunol Today. 1991;  12 49-53
• 8 Romagnani S. Induction of TH1 and TH2 responses: A key role for the “natural” immune response?.  Immunol Today. 1992;  13 379-381
• 9 van Velzen-Blad H, Dijkstra Y J, Schurink G A. et al . Cardiopulmonary bypass and host defense functions in human beings: I. Serum levels and role of immunoglobulins and complement in phagocytosis.  Ann Thorac Surg. 1985;  39 207-211
• 10 DiPiro J T, Howdiesehell T R, Hamilton R G. et al . Immunoglobulin E and eosinophil counts are increased after sepsis in trauma patients.  Crit Care Med. 1998;  26 465-469
• 11 Ginaldi L, De Martinis M, D'Ostilio A, Marini L, Loreto M F, Corsi M P, Quaglino D. The immune system in the elderly: I. Specific humoral immunity.  Immunol Res. 1999;  20 101-108
• 12 Markewitz A, Rothenburger M, Rudolph G, Kuhlmann W D. Humoral immune response following cardiac surgery specific or non-specific activation?.  Shock. 1997;  7 A 105
• 13 DePiro J T, Howdieshell T R, Goddard J K. et al . Association of interleukin-4 plasma levels with traumatic injury and clinical course.  Arch Surg. 1995;  130 1159-1163
• 14 Sherry R M, Cue J I, Goddard J K. et al . Interleukin-10 is associated with the development of sepsis in trauma patients.  J Trauma. 1994;  40 613-617
• 15 Kress H G, Scheidewig C, Schmidt H, Silber R. Reduced incidence of postoperative infection after intravenous administration of an immunoglobulin A- and immunoglobulin M-enriched preparation in anergic patients undergoing cardiac surgery.  Crit Care Med. 1999;  27 1281-1287
• 16 Christou N V. Immunoglobulins in anergic patients: Choice of patients, identification of dependent variables, and importance of study.  Crit Care Med. 1999;  27 1387-1388
• 17 Marggraf G. Adjuvant treatment of mediastinitis with immunoglobulins (Pentaglobin) after cardiac surgery (ATMI): study protocol.  Eur J Surg. 1999;  584 85-100
• 18 Alejandria M M, Lansang M A, Dans L F, Manatring J BV. Intravenous Immunoglobulin for Treating Sepsis and Septic Shock. Update Software, Vol. 3. Oxford; The Cochrane Library 1999
• 19 Heiken H, Schmidt R E. Indikationen für den Einsatz von Immunglobulinen.  Dtsch Med Wochenschr. 2003;  128 1665-1669
• 20 Bone R C. Sir Isaac Newton, sepsis, SIRS, and CARS.  Crit Care Med. 1996;  24 1125-1128

1 Presented at the 4th Joint Meeting of the German, Austrian, and Swiss Society for Thoracic and Cardiovascular Surgery, Hamburg, February 15 - 18, 2004