Eur J Cardiothorac Surg 2002;21:497-501
© 2002 Elsevier Science NL
Detection of thoracotomy-induced alterations in cell- and humoral-mediated immune response
Gulbu Isitmangila*,
Turgut Isitmangilb,
Kunter Balkanlib,
Kamil Cerrahogluc,
Erdogan Kunterc
a Department of Immunology, School of Medicine, Yeditepe University, Istanbul, Turkey
b Department of Thoracic Surgery, Chest Diseases Hospital, Gulhane Military Medical Academy, Istanbul, Turkey
c Department of Chest Diseases, Chest Diseases Hospital, Gulhane Military Medical Academy, Istanbul, Turkey
Received 3 September 2001;
received in revised form 3 December 2001;
accepted 17 December 2001.
* Corresponding author. Tel.: +90-216-5780-529; fax: +90-216-5780-575
e-mail: gulbu{at}hotmail.com
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Abstract
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Objective: It is well known that thoracotomy leads to several complications. In this study, effects of thoracotomy on cellular and humoral immunities have been investigated. Leukocyte counts and lymphocyte counts of 100 patients operated by thoracotomy have been determined preoperatively and on the postoperative 3rd hour, and 1st, 2nd, 3rd, 5th days. Also lymphocyte surface markers (CD3, CD4, CD8, CD4/CD8, CD19, CD16/56) and immunoglobulin levels (IgG, IgA, IgM, IgE) in 40 out of 100 patients in the preoperative period and postoperatively twice on 7th day and then in the 3rd week have been detected. Materials and methods: For the methodology hemocounter, flow cytometer, immunoprecipitation, and enzyme-linked immunosorbent assay were used. Results: A marked increase in leukocyte count while a marked decrease in lymphocyte count has been observed after thoracotomy (P<0.001). There was not any significant alteration in levels of lymphocyte surface markers and immunoglobulins in the postoperative period (P>0.2). Conclusion: According to these results, leucocytosis occurred but lymphocyte count decreased in the early postoperative period. Immunoglobulin levels and subpopulation of lymphocytes were not affected from the operative stress.
Key Words: Thoracotomy • Immune response • Immunity
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1. Introduction
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Surgery depresses host tumoricidal activity and may increase tumor growth [1]. Thoracotomy is a common operative procedure used for diagnosis or therapy of any intrathoracic pathology [2]. Thoracic surgical patients are susceptible to pneumonia because of impaired systemic and lung host defenses [3]. Also many complications concerned with respiratory and circulatory systems have emerged after these operations [4,5]. These complications may be due to impairment of cellular and humoral immune response against thoracic surgery stress. Cellular immunity is mediated by lymphocytes and transferred by the cells of immunized people. Humoral immunity is mediated by antibodies and transferred by the sera of immunized people [6]. Antibodies are immunoglobulin molecules, which are classified as lgG, IgA, IgM, lgD and IgE [7]. Impairment of cellular and humoral immune system may lead to infections secondary to surgery, progression of malign tumors, and emergence of opportunistic infections. In this study, it was aimed to determine the effects of thoracotomy operation on cellular and humoral immune system in different patient groups. In this procedure, lymphocyte surface markers (CD3, CD4, CD8, CD4/CD8, CD19, CD16/56) for cellular immunity detection and immunoglobulin levels (IgG, IgA, lgM, IgE) for humoral immunity detection have been performed. Also leukocyte and lymphocyte counts were analyzed.
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2. Material and methods
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This study has been performed on 100 patients as seven patient groups, which was selected randomly among people operated for thoracotomy at Department of Thoracic Surgery in GMMA Haydarpasa Training Hospital. Patient groups are shown in Table 1. Leukocyte and lymphocyte counts were carried out for all the patients. Ninety-two out of 100 patients were men and the remaining eight were women. The average age was 34.4 years and the patients were in the age range of 18–73 years. Lymphocyte surface markers and immunoglobulin levels were measured in 40 out of the 100 patients. They were randomly chosen from seven patient groups. Male to female ratio in these patients was 7:1 and average age was 36.2 years (range 20–68 years).
A detailed history was taken from the patients by a physician. Physical examination and laboratory analysis were performed routinely. None of them had diabetes mellitus, renal insufficiency, seropositive human immunodeficiency virus (HIV) and other chronic diseases affecting the immune system except for pulmonary or pleural diseases. Previously, there was no history of thoracotomy on all the patients except for tube thoracostomy. Posterolateral thoracotomy was performed on all of the patients except those operated for axillary thoracotomy in Group 1.
Blood samples were obtained from all the patients in the preoperative period (1 day before operation) and postoperative period (3rd hour, 1st day, 2nd day, 3rd day, 5th day after operation) in a 2.5 ml tube containing ethylenediamminetetraacetic acid (EDTA) (Vacutainer). Then they were transported to laboratory within a maximum time 15 min. Leukocyte and lymphocyte counts were measured with Coulter MD 16 heamatologic instrument.
In order to detect humoral immunity, levels of immunoglobulins in the sera indicating the antibody response against thoracic surgery stress were measured. Blood was taken in a 5 ml tube for quantitative immunoglobulin detection. It was collected preoperatively once and postoperatively first on the 7th day and then in the third week from all the patients. Then, it was transferred to the laboratory within approximately 1 h. IgG, lgM and IgA quantitative measurements were made with immunoprecipitation technique using instrument Turbox Orion. For IgE measurement, enzyme-linked immunosorbent assay (ELISA) test assay (Abbot Quantum) was used.
For detection of cellular immune response against thoracic surgery stress, lymphocyte surface markers such as CD3, CD4, CD8, CD4/CD8, CD19 and CD16/56 were determined. For this, 5 ml blood with EDTA was drawn from patients and analyzed with direct method. In summary, 100 µl of blood was added to a combination of a directly conjugated monoclonal antibody with fluorocrom (anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-CD16/56) or isotype control antibodies (DAKO Ltd, UK). After gentle mixing, the samples were left at room temperature for 10 min before addition of 200 µl of FACSlyse solution (Becton Dickinson, UK). Then after gentle resuspension, the samples were incubated for a further 10 min before the addition of 250 µl of 0.2% formaldehyde in phosphate-buffered saline (PBS). Samples were analyzed for flow cytometry (Becton-Dickinson FACScan) within 2–4 h of blood sampling.
2.1. Statistical analysis
Values, given as mean±standard deviation, were calculated with Excel for Microsoft Office 1997 for each group. The significance of differences between preoperative value and each of the postoperative values was tested using Student's t test with a P value of <0.05 being defined as statistically significant.
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3. Results
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There was neither any mortality nor any morbidity. Postoperative complications were wound infection in one patient and persistent air leak (5 days) in another patient. Any surgical operation was not required for these complications.
Leukocyte count increased markedly (+126%) within the initial hours following operation and then it declined gradually on postoperative days. It fell below the level of preoperative value on the 5th postoperative day (Table 2, Fig. 1
). When patient groups were compared, leukocyte count increased markedly in all of them. The greatest increase was in Group 2 patients (+176%) and Group 3 patients (+180%), both of which had a coexisting chronic infection. For leukocyte analysis, there was statistically significant difference in all postoperative measurements except the 5th day (P<0.001).
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Table 2. Mean values ( ), standard deviation values (SD), postoperative alteration percentages and probability values by Student's t test are given for leukocyte and lymphocyte counts in patients with thoracotomya
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Fig. 1. Average values of leukocyte counts for each patient group separately and general average value for 100 patients with thoracotomy at preoperative and postoperative periods (A.T.: axillary thoracotomy, Br.: bronchiectasis, De.: decortication, H.C.: hydatid cyst, Tm.: operable lung cancer, A.Tm.: advanced lung cancer, Aver.: general average value of 100 patients).
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Lymphocyte count increased (+2%) in the initial hours after operation, decreased the next day below the preoperative level (-29%), and then began to increase after postoperative 3rd day (Table 2). For lymphocyte analysis, there was statistically significant difference in all postoperative measurements except the 3rd hour (P<0.001).
There was not any statistically significant difference between preoperative and postoperative values of lymphocyte surface markers (P>0.2). In the same manner, there was not any statistically significant difference between preoperative and postoperative values of immunoglobulins (P>0.2).
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4. Discussion
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We have studied indices of cellular and humoral immunities, which is of relevance, not only with regard to infective complications, but also the influence it may have on the control of malignant disease after various operations on the chest.
The relationship between surgical trauma and immune system has been researched for many years. Abdominal surgical procedures such as laparotomy and laparoscopy were usually studied for surgical trauma in previous studies. Some studies also have been reported about the influence of median sternotomy and open-heart surgery upon the immune system. However, only a few studies have been performed to investigate the effects of thoracotomy on the immune system until now.
Kim et al. reported that total leukocyte count increased and lymphocyte count decreased after operation in patients operated for stages I and II lung cancers [8]. Watanabe et al. determined increase in leukocyte count and decrease in lymphocyte count in 18 patients who had thoracotomy and laparotomy because of esophagus malignancy [9]. Our results are in agreement with these studies with respect to leukocyte and lymphocyte counts.
Kim et al. also reported that CD8 increased and CD4/CD8 ratio decreased [8]. Conversely, Watanabe et al. suggested that thoracotomy led to decrease in CD4+ and CD8+ cells and increase in CD4/CD8 ratio [9]. Ancheva et al. determined a marked decrease in natural killer (CD16/56) cell activity of peripheral blood mononuclear cells after operation of lung cancer patients [10]. Our results are not similar to the above results because we did not find any statistically significant difference between preoperative and postoperative values of CD3, CD4, CD8, CD4/CD8, CD19, and CD16/56 markers.
Watanabe et al. reported a marked decrease in immunoglobulin levels in the first days after thoracotomy [9]. Gebhard et al. analyzed decrease in immunoglobulin levels in 34 patients operated for benign and malignant lung diseases [11]. Conversely in our study, it was determined that thoracotomy did not cause any statistically significant difference between preoperative and postoperative values of immunoglobulins (IgG, IgA, IgM, IgE).
Surgery stress is one of the major factors affecting immune system but indices of cellular and humoral immunities may also be altered by postoperative infections and perioperative blood transfusions. In this study, when patients exposed to surgery stress were taken into account, only one patient had wound infection and none of the patients had pleural space infection and pulmonary infection in the postoperative period. Also totally 13 units of blood were given to 11 out of 100 patients in the perioperative period and so we believe that this low amount of blood transfusions were not enough to affect the immune system of our patients.
Our study suggests that thoracotomy leads to leukocytosis but results in a decrease of lymphocyte counts in the early postoperative period. Among the reasons for leukocytosis, trauma (such as operation, fractures, and burn injury) is one of the leading causes following infectious diseases. In this study, leukocytosis in spite of decrease in lymphocyte count depends upon the increase in neutrophil counts after thoracotomy. There is a neutrophil reserve in the bone marrow and neutrophils are released from bone marrow to the blood in cases of operative stress, infection, and corticosteroid intake.
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5. Conclusions
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This study gives some clues about reactive immune response to surgery stress by increasing inflammatory cells immediately and decreasing lymphocyte counts. However, subpopulations of lymphocytes were not altered by the operative stress showing similar percentages before and after thoracotomy. Also levels of immunoglobulins did not change implying the preservation of humoral immune response during thoracotomy.
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References
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Abstract
1. Introduction
