Effects of murine tumors upon delayed hypersensitivity to dinitrochlorobenzene. IV. Inhibition of elicitation of delayed hypersensitivity

Nonspecific suppressor cells (NSC) from the spleens of tumor-bearing C₃H/HeJ mice when transferred into normal syngeneic mice inhibit primary delayed hypersensitivity responses to dinitrochlorobenzene (DNCB). Previous results suggest that these cells are splenic macrophages since they adhere to plastic, are radioresistant and phagocytic, but Thy 1.2 negative. Experiments were performed to determine if the NSC inhibits the induction or the elicitation phase of the delayed hypersensitivity response. Effector cells were sought in the spleens and lymph nodes of tumor-bearing mice that were previously demonstrated to be hyporesponsive to DNCB in a footpad assay. Ten million spleen or lymph node cells were adoptively transferred to normal mice which were immediately challenged with DNCB in a hind footpad. Measurement of footpads 24 hr later indicated that both spleen and lymph node cells from hyporesponsive tumor-bearing BALB/c and C₃H/HeJ mice transferred DNCB hypersensitivity to syngeneic mice. Similarly, transfer of spleen and lymph node cells from hyporesponsive recipients of NSC also transferred positive footpad responses to normal mice. Kinetic analysis revealed that inhibition of delayed hypersensitivity to DNCB was induced by injection of nonspecific suppressor cells as late as 3, but not at 6 or 9, days after primary sensitization. Cotransfer experiments demonstrated that NSC do not directly inhibit the ability of effector cells to adoptively transfer delayed hypersensitivity to DNCB. Thus, splenic NSC from tumor-bearing mice prevent the elicitation of the efferent phase of delayed hypersensitivity and require at least 7 days residence in the host before mediating this inhibition. Progressive neoplastic outgrowth severely alters the performance of cell-mediated immunity to chemical sensitizers. These results suggest that manipulation of macrophage activity in tumor-bearing hosts may permit expression of immunity to antigens other than those associated with the neoplastic cells.     

Host resistance in sepsis and trauma.

Host resistance to infection was measured by the in vivo response to 5 delayed hypersensitivity antigens and to sensitivity and challenge by dinitrochlorobenzene (DNCB) in 55 seriously ill or injured patients and in 50 preoperative patients. A close correlation between infections, septicemia, death related to infection and anergy was found in the postoperative and post injury patients and was predictive of these complications in the patients studied preoperatively. Decreased body cell mass was noted in both the anergic and non-anergic patients which was consistent with protein-calorie malnutrition but the two groups were not significantly different. A serum factor which inhibited cellular immunity in vitro was found in 4 patients. This factor disappeared in the two patients who recovered. The study suggests the therapeutic value of the in vivo measurement of delayed hypersensitivity in seriously ill and especially preoperative patients in whom specific or non-specific stimulation of cell mediated immunity might alter the risk of infection.     

The value of the DNCB test in bladder cancer. Pretreatment evaluation of immune function and 5-year follow-up of patients with urinary bladder cancer

In 68 patients with histologically verified tumors of the urinary bladder, cell-mediated and humoral immune parameters were investigated before therapy and the results were re-evaluated after a 5-year observation period in order to correlate them with relapse rate and survival time. Skin test reactivity, as measured with recall antigens (tuberculin, streptokinase-streptodornase, mumps, toxoplasmin and candidin), and serum levels of immunoglobulins do not differentiate between levels of invasion and grade of malignancy. However, it was found that patients with tumors of high grades of invasiveness and malignancy were anergic to the primary skin test antigen dinitrochlorobenzene (DNCB). Furthermore, a correlation between anergic reactivity to the DNCB test and absence of local inflammatory reactions at the tumor site was detected, showing that patients with a negative DNCB challenge test were those in whom no immunocytes could be detected in the intra- and peritumoral area. Survival time and incidence of relapse were also correlated with initial skin test reactivity to DNCB, i.e. all patients with tumor stage pT3 and skin test anergy developed recurrences and died within the 5-year observation period. The correlation between morphological inflammatory criteria and immunological parameters detected in patients with advanced tumor stages should therefore be taken into consideration when taking therapeutic decisions at the time of diagnosis.     

Immunologic abnormalities in head and neck cancer

We consider this study only a preliminary exploration into the importance of host immunity in neoplasms of the head and neck. It is evident that a dysfunction of the immune system did occur in these patients, and although regional in origin, these tumors did effect some alterations in the systemic cellular immune function as measured by DNCB reactivity. Sequential variations in the degree of effect on immunity occurred and these alterations were correlated with the patient's subsequent clinical course. Conversion from positive to negative reactions was observed if control of the tumor was not achieved. Therefore, it is very unlikely that a pre-existent defect in immunity was the principal determinant of disease progression.It must be emphasized that these evaluations are concerned with nonspecific immunity and not with immunity to tumor-specific antigens. Certainly both specific and nonspecific immune reactions are very important in other non-neoplastic bacterial and viral diseases. Studies are now under way to evaluate tumor-specific immune reactions and to determine if nonspecific stimulants of immunity such as BCG can alter the immunologic reactivity and, therefore, affect the clinical course of patients with neoplasms of the head and neck.     

Immunologic Response After Laparoscopic Colon Cancer Operation Within an Enhanced Recovery Program

Objective

It has been demonstrated that colon operation combined with fast-track (FT) surgery and laparoscopic technique can shorten the length of hospital stay, accelerate recovery of intestinal function, and reduce the occurrence of post-operative complications. However, there are no reports regarding the combined effects of FT colon operation and laparoscopic technique on humoral inflammatory cellular immunity.

Methods

This was a prospective, controlled study. One hundred sixty-three colon cancer patients underwent the traditional protocol and open operation (traditional open group, n?=?42), the traditional protocol and laparoscopic operation (traditional laparoscopic group, n?=?40), the FT protocol and open operation (FT open group, n?=?41), or the FT protocol and laparoscopic operation (FT laparoscopic group, n?=?40). Blood samples were taken prior to operation as well as on days 1, 3, and 5 after operation. The number of lymphocyte subpopulations was determined by flow cytometry, and serum interleukin-6 and C-reactive protein levels were measured. Post-operative hospital stay, post-operative morbidity, readmission rate, and in-hospital mortality were recorded.

Results

Compared with open operation, laparoscopic colon operation effectively inhibited the release of post-operative inflammatory factors and yielded good protection via post-operative cell immunity. FT surgery had a better protective role with respect to the post-operative immune system compared with traditional peri-operative care. Inflammatory reactions, based on interleukin-6 and C-reactive protein levels, were less intense following FT laparoscopic operation compared to FT open operation; however, there were no differences in specific immunity (CD3+ and CD4+ counts, and the CD4+/CD8+ ratio) during these two types of surgical procedures. Post-operative hospital stay in patients randomized to the FT laparoscopic group was significantly shorter than in the other three treatment groups (P?P?Conclusions The laparoscopic technique and FT surgery rehabilitation program effectively inhibited release of post-operative inflammatory factors with a reduction in peri-operative trauma and stress, which together played a protective role on the post-operative immune system. Combining two treatment measures during colon operation produced better protective effects via the immune system. The beneficial clinical effects support that the better-preserved post-operative immune system may also contribute to the improvement of post-operative results in FT laparoscopic patients.     

The spleen as a source of nonspecific suppressor cells in the tumor-bearing mouse

Tumor-bearing (TB) mice are anergic to the development of hypersensitivity to simple chemical agents like dinitrochlorobenzene (DNCB). This anergy may provide a model for the unresponsiveness described in cancer patients. When mice with progressive growth of an antigenic tumor are sensitized to DNCB, they fail to display delayed-type hypersensitivity (DTH). On the other hand, hosts which undergo spontaneous regression of neoplasms develop DTH to DNCB normally. The nature of the anergy to tumor bearers was investigated in systemic adoptive transfer experiments: intraperitoneal inoculation of spleen cells harvested from TB mice not treated with DNCB nonspecifically inhibited sensitization of normal mice to this hapten. The splenic suppressor cells were present 10 days after tumor inoculation. Fractionation on plastic surfaces revealed the suppressor cells reside in the adherent cell population. Investigation of the mechanisms of anergy to DNCB in mice may provide insights into the state of anergy in cancer patients.     

Delayed hypersensitivity reactions in patients with squamous cell cancer of the head and neck

Sixty-three patients with squamous cell cancer of the head and neck were evaluated, correlating TNM class with delayed hypersensitivity reactions. These cell-mediated immune responses were impaired early in the course of the disease. Eight of twenty-four patients with T₁ or T₂ N₀ lesions were DNCB-negative. With more advanced lesions, reactivity was further impaired. Only one of six patients with T₃ or T₄ N₀ lesions was DNCB-positive. There is an impaired response not only to newly encountered antigens but also to previously encountered antigens.There was a correlation between DNCB reactivity, recurrence, and survival in patients with localized disease. There was also similar correlation of PPD reactivity and survival at the one year level. In the presence of cervical node metastases, there was no apparent difference in recurrence or survival related to DNCB reactivity.Skin test reactivity to DNCB in patients with head and neck cancer has apparent prognostic implications and may be of use in patient management.     

Effects of albumin on serum protein homeostasis after hypovolemic shock

The effects of albumin on serum protein homeostasis were studied prospectively in 52 seriously injured patients who received an average of 15.3 transfusions, 9.7 liters of electrolyte solution, and 1 liter of fresh frozen plasma before and during operation. Based on randomization, 27 patients received an average of 25 g of albumin during operation followed by 150 g/day for 5 days, thereafter; 25 patients received no albumin. The cause of injury, volume needs during resuscitation, and severity of shock were similar for both groups. Sequential serum levels of total protein, albumin, α¹-globulin, α²-globulin, β-globulin, γ-globulin, and fibrinogen and hourly disappearance of radioactive iodinated serum albumin (RISA) were measured for comparison. Patients given albumin had a significant (P < 0.05) increase in total protein and albumin levels throughout the first 6 days after operation. α¹-Globulin levels were similar in both groups. In contrast, α²-globulin, β-globulin, γ-globulin, and fibrinogen levels were significantly decreased throughout the postoperative period in those patients receiving albumin. The hourly disappearance of labeled albumin was also increased in patients receiving albumin. These changes probably reflect a redistribution of albumin and globulin fractions in response to shock, although decreased production cannot be ruled out.Altered hemostasis and depressed immune response are two possible effects with clinical significance. Plasma volume and serum albumin concentration describe only the primary effect of albumin supplementation. Additional investigation of secondary homeostatic responses are necessary to more completely evaluate the effects of albumin infusion.     

Lymphocyte function in the critically ill surgical patient

Lymphocyte function is commonly altered in critical ill surgical patients. There is controversy whether or not formation of antibodies is impaired; however, cellular immune responses are routinely depressed. Patients who have suffered major surgical or accidental trauma or burns frequently become anergic. Their lymphocytes respond poorly to mitogenic or antigenic stimulation, and serum factors suppressive of lymphocyte activation appear. Mechanisms underlying these abnormalities remain to be defined.     

Variation in T helper cell/T cytotoxic-suppressor cell index during cardiac operations

After surgical procedures, humoral and cell-mediated immunity responses decrease. Both anesthesia and surgical trauma play an important role in this effect. Cardiac operations induce a greater decrease in immunologic response than other surgical operations. On the other hand, identification of functional lymphocyte subclasses by means of appropriate monoclonal antibodies appears to provide an accurate measurement of cellular immune competence. Employing these methods, we found a significant decrease of T helper cell/T cytotoxic-suppressor cell ratio in the periperal blood of 20 patients undergoing cardiac operations. This decrease during the period of anesthesia (before surgical incision) is due as much to a decrease of T helper cell percentage as to an increase of T cytotoxic cell percentage. However, during the surgical trauma period (surgical incision to the end of the operation) it is due to a greater increase of T cytotoxic-suppressor cell percentage without significant changes in the percentage of T helper cells.     

Delayed-type hypersensitivity (DTH) test anergy does not impact CD4 reconstitution or normalization of DTH responses during antiretroviral therapy

Introduction

Delayed-type hypersensitivity (DTH) testing is an in vivo assessment of cell-mediated immunity. Although highly active antiretroviral therapy (HAART) improves immunologic parameters, the relationship between DTH responsiveness and CD4 gains on HAART is not completely understood. We investigated CD4 reconstitution and the change in DTH responses from treatment baseline through 24 months of viral load (VL)-suppressive HAART in the U.S. Military HIV Natural History Study.

Methods

Treatment-naïve subjects with VL <400 copies/mL after ≥24 months on HAART were included (n=302). DTH testing consisted of ≥3 recall antigens, and responses were classified by the number of positive skin tests: anergic (0–1) or non-anergic (≥2). Pre-HAART DTH results were compared for the outcome of CD4 reconstitution at 24 months of HAART. Improvement in DTH responses was also analyzed for those anergic before HAART initiation.

Results

Non-anergic responses were observed in 216 (72%) participants, while 86 (28%) individuals were anergic prior to HAART initiation. Demographically there were similar distributions of age at HIV diagnosis and HAART initiation, as well as gender and race or ethnicity. There were no significant differences between non-anergic and anergic participants in pre-HAART CD4 count (409 cells/μL, interquartile range (IQR) 315–517 vs. 373 cells/μL, IQR 228–487; p=0.104) and VL (4.3 log₁₀ copies/mL, IQR 3.4–4.9 vs. 4.4 log₁₀ copies/mL, IQR 3.6–5.0; p=0.292). Median CD4 gains 24 months after HAART initiation were similar between the non-anergic (220 cells/μL, IQR 115–358) and anergic groups (246 cells/μL, IQR 136–358; p=0.498). For individuals anergic before HAART initiation, DTH normalization occurred at 24 months post-HAART in the majority of participants (51 of 86, 59%). Normalization of DTH responses was not associated with CD4 count at HAART initiation (OR 0.73, 95% CI 0.47, 1.09 per 100 cells; p=0.129) nor with AIDS diagnoses prior to HAART (OR 0.34, 95% CI 0.04, 2.51; p=0.283).

Conclusions

DTH responsiveness has been shown to predict HIV disease progression independent of CD4 count in untreated individuals. In the setting of HAART, pre-HAART anergy does not appear to impact CD4 gains or the ability to normalize DTH responses after 24 months of VL-suppressive HAART.     

T-cell deficiency in patients with squamous cell cancer of the head and neck

Cellular immunity was assessed in patients with operable squamous cell cancer of the head and neck using in vivo skin tests and in vitro lymphocyte stimulation tests. An expansion of a previous study continued to show that 30 per cent of patients with T₁N₀M₀ lesions were DNCB-negative and that with more advanced lesions there was further impairment. A similar finding was observed in the blastogenic response to phytohemagglutinin and conconavalin A but not pokeweed mitogen. Overall, 40 per cent of patients with resectable cancer had a significant depression of the blastogenic responses to conconavalin A and phytohemagglutinin. This depression ranged from 15 per cent in patients with T₁N₀M₀ lesions to 71 per cent in those with T₃N₀M₀ lesions. Although this depression was more severe in patients with palpable cervical node metastases, it was related more to the size of the primary tumor than to the nodes per se. An exception occurred in patients with large fixed nodes in whom the depression of lymphocyte stimulation was most severe. The absolute T-cell count was also depressed in patients with head and neck cancer. This depression parallelled the lymphocyte stimulation results with phytohemagglutinin and conconavalin A and was progressive with increasing stage of disease.A correlation exists between DNCB negativity and early recurrence and shortened survival. Clinical follow-up study is too short to assess the correlation of in vitro immune function with these clinical prognostic factors.     

Lymphocyte response after surgery and blood transfusion

This study presents further evidence that there is a depression of cellular immune function after surgical trauma. Cellular immune function was measured by the degree of mitogenic transformation of peripheral blood lymphocytes. The significant reduction (P < 0.02) in lymphocyte transformation seen after surgery was partly reversed in those patients transfused with blood during operation. In a group of medical patients there was a significant increase above the normal level (P < 0.02) in lymphocyte transformation seen after surgery, and this was partly reversed in these patients transfused with blood during operation. In a group of medical patients there was a significant increase above the normal level (P < 0.02) in lymphocyte transformation after transfusion.     

Severe Acute Respiratory Syndrome Coronavirus 2 Cross-Reactive B and T Cell Responses in Kidney Transplant Patients

BackgroundImmune responses to seasonal endemic coronaviruses might have a pivotal role in protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Those SARS-CoV-2-crossreactive T cells were recently described in immunocompetent individuals. Still, data on cross-reactive humoral and cellular immunity in kidney transplant recipients is currently lacking.MethodsThe pre-existing, cross-reactive antibody B and T cell immune responses against SARS-CoV-2 in unexposed adults with kidney transplantation (Tx, n = 14) and without (non-Tx, n = 12) sampled before the pandemic were compared with 22 convalescent patients with COVID-19 (Cp) applying enzyme-linked immunosorbent assay and flow cytometry.ResultsIn both unexposed groups, SARS-CoV-2 IgG antibodies were not detectable. Memory B cells binding spike (S) protein SARS-CoV-2 were detected in unexposed individuals (64% among Tx; 50% among non-Tx) and higher frequencies after infection (80% Cp). The numbers of SARS-CoV-2-reactive T cells were comparable between patients who had undergone Tx and those who had not. SARS-CoV-2-reactive follicular T helper cells were present in 61% of the unexposed cohort in both patients who had undergone Tx and those who had not.ConclusionsCross-reactive memory B and T cells against SARS-CoV-2 exist also in transplanted adults, suggesting a primed adaptive immunity. The effect on the disease course may depend on the concomitant immunosuppressive drugs.     

Delayed Hypersensitivity: Indicator of Acquired Failure of Host Defenses in Sepsis and Trauma

Primary failure of host defense mechanisms has been associated with increased infection and mortality. Anergy, the failure of delayed hypersensitivity response, has been shown to identify surgical patients at increased risk for sepsis and related mortality. The anergic and relatively anergic patients whose skin tests failed to improve had a mortality rate of 74.4%, whereas those who improved their responses had a mortality rate of 5.1% (P < 0.001). This study documents abnormalities of neutrophil chemotaxis, T-lymphocyte rosetting in anergic patients and the effect of autologous serum. These abnormalities may account for the increased infection and mortality rates in anergic patients. Skin testing with five standard antigens has identified 110 anergic (A) or relatively anergic (RA) patients in whom neutrophil chemotaxis (CTX) and bactericidal function (NBF), T-lymphocyte rosettes, mixed lymphocyte culture (MLC), cell-mediated lympholysis (CML), and blastogenic factor (BF) were studied. The MLC, CML and BF were normal in the patients studied, and were not clinically helpful. Neutrophil CTX in 19 controls was 117.5 +/- 1.6 u whereas in 40 A patients, neutrophils migrated 81.7 +/- 2.3 u and in 15 RA patients 97.2 +/- 3.8 u (P < 0.01). In 14 patients whose skin tests converted to normal, neutrophil migration improved from 78.2 +/- 5.4 u to 107.2 +/- 4.0 u (P < 0.01). Incubation of A or control neutrophils in A serum reduced migration in A patients from 93 +/- 3.7 u to 86.2 +/- 3.5 u (P < 0.01) and in normals from 121.2 +/- 1.6 u to 103.6 +/- 2.6 u (P < 0.001). The per cent rosette forming cells in 66 A patients was 42.5 +/- 3.1 compared to 53.6 +/- 2.8 in normal responders (P < 0.02). Incubation of normal lymphocytes in anergic serum further reduced rosetting by 30%. Restoration of delayed hypersensitivity responses and concurrent improvement in cellular and serum components of host defense were correlated with maintenance of adequate nutrition and aggressive surgical drainage.     

Thymostimulin immunoprophylaxis in elective abdominal surgery]

The Authors report their experience of 121 patients who had undergone an elective abdominal operation and who had been previously considered under an immunological point of view and classified as anergic. The Authors have found a notable reduction of postoperative infection incidence in the 61 anergic operated patients who have been treated with Thymostimulin; they conclude by underlining the importance of careful consideration and eventual correction of immunological alterations of the patients of the patients who must undergo an operation.     

Monitoring of immunosuppression in beagles.

The effects of immunosuppressive drugs were measured after 2, 5, and 9 months of treatment during canine bronchial carcinogenesis experiments. Antibody titers to bovine red blood cells, rat blood cells, and chicken γ-globulin were determined, and skin allografts were used to test levels of immunity. Delayed cutaneous hypersensitivity responses to rabies vaccine, combination distemper-hepatitis-leptospirosis vaccine, and 3,5-dinitrochlorobenzene (DNCB) were evaluated. Absolute lymphocyte counts were the most sensitive dose-related nonspecific indicators of the level of immunosuppression. High dose immunosuppression (HIS) with azathioprine, 2.5 mg/kg/day, and methylprednisolone, 1.0 mg/kg/day, depressed antibody responses within 2 months (P < 0.01). HIS also prolonged skin allograft rejection from 6.5 ± 0.9 to 14.1 ± 1.1 days (P < 0.01), and it suppressed cutaneous responses to distemper vaccine and DNCB (P < 0.01). Most beagles could not tolerate HIS chronically under the conditions of our experiments.Low dose immunosuppression (LIS) at one-half the HIS level was well tolerated. LIS prolonged skin allograft rejection to 10.8 ± 1.0 days (P < 0.01), and it also suppressed cutaneous hypersensitivity (P < 0.01). LIS inhibited antibody responses after 9 months of treatment (P < 0.01), but not after 2 months of therapy. All of the skin tests provided evidence of immunosuppression but none did so consistently. Distemper vaccine gave the clearest responses.We conclude that an approach which quantitates immunosuppression in dogs has broad practical applicability to canine transplantation and carcinogenesis research.     

Efeitos do bloqueio peridural caudal em pacientes cirúrgicos pediátricos: estudo randomizado

BackgroundSurgery generates a neuroendocrine stress response, resulting in undesirable hemodynamic instability, alterations in metabolic response and malfunctioning of the immune system.ObjectivesThe aim of this research was to determine the effectiveness of caudal blocks in intra‐ and postoperative pain management and in reducing the stress response in children during the same periods.MethodsThis prospective, randomized clinical trial included 60 patients scheduled for elective herniorrhaphy. One group (n = 30) received general anesthesia and the other (n = 30) received general anesthesia with a caudal block. Hemodynamic parameters, drug consumption and pain intensity were measured. Blood samples for serum glucose and cortisol level were taken before anesthesia induction and after awakening the patient.ResultsChildren who received a caudal block had significantly lower serum glucose (p < 0.01), cortisol concentrations (p < 0.01) and pain scores 3 hours (p = 0.002) and 6 hours (p = 0.003) after the operation, greater hemodynamic stability and lower drug consumption. Also, there were no side effects or complications identified in that group.ConclusionsThe combination of caudal block with general anesthesia is a safe method that leads to less stress, greater hemodynamic stability, lower pain scores and lower consumption of medication.     

Serum glycoproteins in head and neck squamous carcinoma: correlations with tumor extent, clinical tumor stage, and T-cell levels during chemotherapy.

In patients with solid malignancies, serum levels of specific acute phase proteins (haptoglobin, α₁-acid glycoprotein, and α₁-antitrypsin) have been correlated with parameters of both tumor extent and cellular immunity, while α₂HS-glycoprotein and prealbumin have been correlated with parameters of cellular immunity. To determine the relation of the glycoproteins to these parameters in head and neck squamous carcinoma, serum levels were measured in 90 untreated patients, 51 cured patients, 11 patients with recurrent carcinoma, and 20 patients during preoperative chemotherapy. The control patients were 139 chronic cigarette smokers.Haptoglobin levels were significantly increased in patients with stage I through IV tumors (AJC-1977), but levels were similar for each stage. Serum levels of α₁-antitrypsin and α₁-acid glycoprotein increased progressively with increasing tumor stage. Serum α₂HS-glycoprotein, prealbumin, and albumin levels were decreased in all patients, and α₁HS-glycoprotein levels decreased progressively with increasing tumor stage. When patients were classified into those with local tumors only and those with regional metastases, and further subclassified by extent of local or regional tumor, the acute phase proteins generally increased with increasing local or regional tumor extent and α₂HS-glycoprotein levels tended to decrease in the same groups. In cured patients, haptoglobin and α₁-acid glycoprotein levels were significantly lower and α₂HS-glycoprotein and prealbumin significantly higher than in untreated patients. Protein levels in patients with recurrent tumors were similar to levels in untreated patients. During acute immunosuppressive chemotherapy, levels of T-cells and α₂HS-glycoprotein decreased significantly and similarly, and after completion of chemotherapy, rebounded to pretreatment levels, while α₁-antitrypsin levels increased and haptoglobin and α₁-acid glycoprotein levels did not change.The data show that α₁-antitrypsin and α₁-acid glycoprotein correlate better with AJC tumor stage than cellular immune parameters previously studied and that α₂HS-glycoprotein levels may be as useful as T-cell levels for monitoring immune reactivity in patients with squamous cancer of the head and neck. These results suggest the potential of these biologic parameters as adjuncts in the derivation of improved staging systems and as indicators of tumor status and immune reactivity in patients with squamous carcinoma of the head and neck.     

Prostaglandin el 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 El (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. (Jpn J Thorac Cardiovasc Surg 2006; 54:149-154)