Tetsuro Sano

Minor Infection Encouraged by Steroid Administration during Cardiac Surgery

The aim of this study was to investigate whether steroid administration would increase the risk of postoperative infection. Sixty adults who underwent elective cardiac surgery under cardiopulmonary bypass were prospectively randomized into two groups. Thirty-one patients received hydrocortisone (50 mg·kg−1) before and after cardiopulmonary bypass, the other 29 served as controls. Various hemodynamic and pulmonary measurements were obtained perioperatively, and the white blood cell counts and levels of C-reactive protein were checked up to the 14th postoperative day. Steroid administration did not have any favorable effects during the perioperative period. Re-administration of antibiotics was needed in 7 patients (22.6%) after the 7th postoperative day in the steroid group, and in 3 (10.3%) in the control group. The peak white cell counts and C-reactive protein levels after the 7th postoperative day were significantly higher in the steroid group. Steroid administration offered no clinical benefit to patients undergoing cardiac surgery with cardiopulmonary bypass, and it may encourage minor infections in the late postoperative period.

Comparative analysis of HLA restriction and cytokine production in hepatitis B surface antigen-specific T cells from low- and high-antibody responders in vaccinated humans.

AbstractIt is well known that individuals with low, or lack of, antibody production in response to hepatitis B surface antigen (HBsAg) exist in the human population. We have previously reported that HLA class I and class II genes are both involved in antibody production to HBsAg, and that specific alleles of HLA are associated with low and high antibody production. To elucidate further the mechanisms by which the diversity of antibody production to HBsAg is generated in humans, a total of 146 T-cell clones specific for HBsAg were produced from six healthy vaccinees (three low- and three high-antibody responders) and were examined for cytokine production and HLA restriction. It was found that the majority of the T-cell clones from the low-antibody responders were Th1- or Th0-like T cells (62% or 19%, respectively), whereas the majority of T-cell clones from the high-antibody responders were Th2-like T cells (77%), suggesting predominant expansion of Th1/Th0- and Th2-like T cells specific for HBsAg in the low- and high-antibody responders, respectively. This is the first evidence that the diversity of the response to HBsAg in humans is controlled by the activation of functionally distinct CD4+ T-cell subsets, i.e., Th0, Th1, or Th2 T cells.

Cardiopulmonary bypass, steroid administration, and surgical injury synergistically impair memory T cell function and antigen presentation

Previous reports showed that cardiac surgery with cardiopulmonary bypass (CPB) impair cell-mediated immunity by using antigen-non-specific responses. This study elucidated the effects of cardiac surgery with CPB on antigen-specific immunity. Twenty patients who underwent elective cardiac surgery using CPB were randomly divided into two groups: group A (n=10) and group B (n=10) with and without steroid administration, respectively. Group C patients underwent off-pump CABG (n=8). Peripheral blood mononuclear cells (PBMCs) were taken before and after surgery. Proliferation responses to pure protein derivative antigen were measured. The effects of CPB and steroid on T cell response and antigen-presentation were assessed by cross-stimulation between the preoperative and the postoperative PBMCs. Antigen-specific T cell responses decreased to about 5% of the preoperative values immediately after surgery with CPB, regardless of steroid administration. The T cell response in group B on POD 7 was significantly higher than that in group A. CPB impaired mainly T cell responses, and steroid administration enhanced impairment of T cell response and antigen-presentation. Open-heart surgery with CPB severely impaired antigen-specific immunity. Steroid administration enhanced the impairment of antigen-presentation as well as T cell function, and retarded the recovery of antigen-specific immunity.

Adaptive immunity is severely impaired by open-heart surgery.

OBJECTIVE The influence of open-heart surgery on antigen-specific immunity, also called adaptive immunity, remains to be clarified. We explored the effects of open-heart surgery on adaptive immunity. METHODS In 8 consecutive adult patients undergoing elective cardiac surgery with cardiopulmonary bypass, we measured the T cell-response to purified protein derivative (PPD) antigen perioperatively. We separately measured the proliferation of T cells and the antigen presentation of antigen-presenting cells (APCs) using a cross-reaction system. RESULTS T cell response to PPD antigen was severely impaired by open-heart surgery. Compared to preoperative values, T cell response to PPD antigen fell to 5.7 +/- 4.4% immediately after surgery, 4.5 +/- 3.2% on postoperative day (POD) 1, to 22.4 +/- 24.6% on POD 3 and to 50.1 +/- 34.3% on POD 7. T cell proliferation on POD1 decreased to 29 +/- 26%. APC antigen-presentation on POD 1 also decreased to 31 +/- 36%. CONCLUSIONS Open-heart surgery impaired both T cell proliferation and the antigen-presentation. Such synergistic impairment severely impaired adaptive immunity. This impairment was both severer and longer than we anticipated based on previous studies using the response of T cells to lectin as a marker of cell-mediated immunity.

Prostaglandin E1 attenuates impairment of cellular immunity after cardiopulmonary bypass.

OBJECTIVE It is well documented that cardiopulmonary bypass (CPB) severely impairs cellular immunity. The objective of this study was to investigate the effect of prostaglandin E1 (PGE1) on cellular immunity after CPB. METHODS Patients who underwent elective cardiac surgery were randomly divided into the PGE1 group (n=12) and the control group (n=12). In the PGE1 group, PGE1 was administered at 20 ng/kg/min from just after the induction of anesthesia to the end of surgery. Peripheral blood mononuclear cells (PBMCs) were taken before anesthesia and on postoperative days 1, 3 and 7 (POD 1, POD 3 and POD 7). Proliferation responses of T cells to phytohemagglutinin (PHA) and pure protein derivative (PPD) antigen were measured as indicators of cellular immunity. RESULTS PGE1 significantly attenuated the impairment of both PHA and PPD response after cardiac surgery on POD 1 (PHA response, 30 +/- 21% vs. 53 +/- 32%, control vs. PGE, p=0.048; PPD response, 18 +/- 21% vs. 39 +/- 27%, control vs. PGE, p=0.046). The reduced glutathione content of PBMCs in the control group was significantly decreased on POD 1. CONCLUSION PGE1 attenuated the impairment of cellular immunity after cardiac surgery with CPB by reducing oxidative stress on PBMCs.

Spontaneous clustering of Thy‐1 antigens on CD4+CD8+ thymocytes lacking TCR engagement by MHC / peptide complexes

While much is known concerning CD4+CD8+ thymocytes positively or negatively selected through interaction of their TCR with self peptides bound to self‐MHC molecules, little is known of the majority of CD4+CD8+ thymocytes lacking this interaction. We developed a monoclonal antibody (mAb) 1D11, the ligand of which (1D11‐L) is expressed on 60 – 70 % of CD4+CD8+ thymocytes but not on other subsets of thymocytes and peripheral T cells. 1D11‐L expression on CD4+CD8+ thymocytes reversely correlates with their TCR engagement, in vitro and in vivo. In addition, 1D11‐L+CD4+CD8+ thymocytes were more susceptible than 1D11‐L–CD4+CD8+ thymocytes to apoptosis. We also found that T lineage cells other than CD4+CD8+ thymocytes and a Thy‐1‐expressing fibroblast cell line became positive for 1D11‐L by cross‐linking their Thy‐1 antigens with anti‐Thy‐1 mAb but not with their Fab fragment, suggesting that 1D11 recognizes multimerized Thy‐1 antigens. Confocal laser scanning microscopy revealed that Thy‐1 antigens as well as 1D11‐L are clustered on some CD4+CD8+ thymocytes but not on the other subsets of thymocytes. Taken together, we suggest that clustering of Thy‐1 antigens spontaneously and specifically occurs on CD4+CD8+ thymocytes lacking TCR engagement by MHC / peptide complexes.