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- Seven patients with solitary or bilateral renal carcinoma were treated surgically over a 7-year period. Ten kidneys were operated upon, 3 by in situ partial nephrectomy, 3 by autotransplantation following bench surgery, 3 by radical nephrectomy and one by simple nephrectomy. Four of the 6 patients treated by partial nephrectomy are alive without disease with an average follow-up of 3½ years. By detailed selective renal arteriography we can usually predict pre-operatively the appropriate operation. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study., Objective: To report the clinical and radiological outcomes for screw track augmentation with fibular allograft in revision of loose pedicle screws associated with significant bone loss along the screw track., Methods: Thirty consecutive patients, 18 men (60%) and 12 women (40%), with a mean age 52 years (range 34- 68). Fibular allograft was prepared by cutting it into longitudinal strips 50 mm in length. Three allograft struts were inserted into the screw track. Six mm tap used to tap between the 3 fibular struts. Eight- or 9-mm diameter, and 45 or 50 mm in length screw was then inserted. The clinical outcomes were assessed by means of the Oswestry Disability Index (ODI), and visual analog scale (VAS) for back and leg pain for clinical outcome. Computed tomography scan (CT) performed at 12 months postoperative visit to assess fibular graft incorporation along the pedicle screw track, any screw loosening and the interbody as well as posterolateral fusion., Results: At a mean follow up of 29 months, there were statically significant improvement in the ODI and VAS for back and leg pain. CT scan obtained at last follow-up showed incorporation of fibular allograft and solid fusion in all patients except one., Conclusion: The fibular allograft augmentation of the pedicle screw track in revision of loose pedicle screws associated with significant bone loss is a viable option. It allows for biologic fixation at the screw-bone interface and has some key advantages when compared to currently available methods.

Purpose: The presence of soft tissue injury in pediatric supracondylar humerus fractures (SCHFs) has been shown to be an independent predictor of any neurovascular injury. Potentially expanding this concept, the specific neurovascular structure injured around the elbow is thought to be dependent upon the direction and magnitude of fracture displacement and subsequent soft tissue injury. Therefore, it was hypothesized that the bruise location following SCHF is indicative of the anatomic location of maximal soft tissue injury and therefore is a specific prognosticator of which neurovascular structure may be injured., Methods: Retrospective chart review of all SCHFs treated at a tertiary pediatric hospital from 2007 to 2017 collected information on bruise location, neurovascular injury patterns, and outcomes. Bruise location was classified as anterior, anterolateral, anteromedial, or posterior. Injury radiographs were reviewed by a blinded pediatric orthopaedic surgeon to neurovascular structure injured., Results: Of 2845 SCHFs identified, 267 (9.4%) had concomitant neurovascular injury-of which 128 (47.9%) met inclusion criteria. Among the vascular injuries, all bruising was anteromedial (28/45, 62.2%, P<0.05) or anterior (17/45, 37.8%, P>0.05). Fractures with anteromedial bruising correlated with median nerve injury (24/27, 88.9%, P<0.05), whereas fractures with anterolateral bruising correlated with radial nerve injuries (24/25, 96.0%, P<0.05). Bruising or radiographic evaluation correctly identified 60.2% and 64.1% of neurovascular injuries, respectively, whereas the combination identified 82.0% of neurovascular injuries correctly. Bruise location identified 23 neurovascular injuries not predicted by radiographic evaluation alone., Conclusion: Bruise location is an important physical examination finding that can be used as an adjunct to improve the diagnostic accuracy of neurovascular injury in SCHFs in conjunction with neurovascular physical examination and radiographic evaluation. SCHFs with anterior or anteromedial bruising should raise concern for vascular injury. In addition, anteromedial bruising is predictive of a median nerve injury and anterolateral bruising is predictive of radial nerve injury. This adjunct diagnostic is particularly helpful in a noncooperative child or if performed by a clinician with limited experience in diagnosing neurovascular injuries or interpreting pediatric elbow radiographs., Level of Evidence: Level IV, case series., Competing Interests: J.G.S. receives research funding from OrthoPediatrics, served as a board member of Pediatric Society of North America (POSNA) and research support from IONIS Pharmaceuticals. The remaining authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Study Design: Retrospective chart review., Objective: Determine if there is a subset of presumed infantile idiopathic scoliosis (IIS) patients who have a low incidence of neural axis abnormalities (NAAs) such that screening magnetic resonance imaging (MRI) may be delayed., Summary of Background Data: Individuals with presumed IIS have an increased incidence of NAA. Because of the increased incidence, screening MRI is recommended for all patients. We follow these guidelines at our institution. However, MRI screening in this age group is not without cost or risk., Methods: This is a retrospective study of 53 presumed IIS (onset ≤3 years) patients who had screening MRIs. Demographic and radiographic characteristics were collected. A binary regression using continuous and categorical variables was used to determine if a model could be created to accurately predict MRI necessity. A receiver operating characteristic (ROC) analysis was performed to determine if a threshold Cobb angle exists that is associated with an increased likelihood of NAA., Results: Of the 53 patients, 13 had NAA findings, resulting in a 24.5% incidence of NAAs. Significantly fewer abnormal MRIs were found in patients with Cobb angles <29.5° than those with Cobb angles >29.5° (13/33 [39%] vs. 0/20 [0%], p = .0008). Patients with Cobb angles >29.5° were 27 times more likely to have NAAs than those with angles <29.5° (odds ratio = 27.0 [95% CI = 1.5-486.0], p = .03). No other parameters have a predictive value for NAA (p > .05)., Conclusion: This is the first study in IIS patients to identify a radiographic parameter that helps select out a subgroup for MRI screening. Additionally, we report an incidence of 24.5% NAAs in these patients, which is higher than previously reported., (Copyright © 2018 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Surgeons have always played an integral role in the history of the Albany Medical Center and Albany Medical College. In addition to supporting vital patient care and teaching programs, the Department of Surgery has played an important administrative role providing the college with five deans. The origins of the Department of Surgery reach back to 1910 when the American Medical Association-sponsored Flexner report proposed dramatic changes in the structure and format of medical education in the United States. In response to the recommendations of the report, the medical center restructured its faculty and curriculum to meet the demands of a rapidly advancing profession. One result of this reorganization was the formation of the Department of Surgery in 1912. Dr. Arthur Elting was named the first Chair of the Department in 1915. This report will review the history of the Department, focusing on the eight surgeons who have served as Chair.

Purpose: Colonic perforations in renal transplant recipients have historically been associated with mortality rates as high as 50 to 100 percent. However, these previous series generally predate the use of cyclosporine-based immunosuppressive protocols., Methods: We retrospectively reviewed all patients who had undergone renal transplant from our institution and who developed complicated diverticulitis. Complicated diverticulitis was defined as diverticulitis involving free perforation, abscess, phlegmon, or fistula. Factors analyzed included the time interval since transplantation, use of cyclosporine, living-related vs. cadaveric donor, cause of renal failure, and presenting signs and symptoms., Results: Between August 1969 and September 1996, 1,211 kidney transplants were performed in 1,137 patients. The first 388 patients (1969-1984) received prednisone and azathioprine, with cyclosporine added to the immunosuppressive regimen for the subsequent 823 recipients (1984-1996). Thirteen (1.1 percent) patients had episodes of complicated diverticulitis, occurring from 25 days to 14 years after transplant; all required surgical therapy. Clinical presentation was highly variable, ranging from asymptomatic pneumoperitoneum (2 patients) to generalized peritonitis. There was one perioperative mortality (7.7 percent). Patients with polycystic kidney disease as the cause of renal failure had a significantly higher rate of complicated diverticulitis. Specifically, patients with polycystic kidney disease (9 percent of the total transplant population) accounted for 46 percent of the cases of diverticulitis (P < 0.001, Fisher's exact probability test). Neither treatment with cyclosporine nor donor source had a significant effect on the rate of diverticular complications (P = 0.36 and P = 0.99, respectively, Fisher's exact probability test)., Conclusion: Complicated diverticulitis following renal transplantation is rare, and the clinical presentation may be atypical in the immunosuppressed transplant recipient. Patients with polycystic kidney disease experience a significantly higher rate of complicated diverticulitis than do other transplant patients and, therefore, warrant aggressive diagnostic evaluation of even vague abdominal symptoms. In addition, pretransplant screening and prophylactic sigmoid resection in this high-risk population deserve consideration and further study.

Cyclosporin G (CSG) has produced less nephrotoxicity than cyclosporin A (CSA) at equivalent doses in animal models. Conflicting results have been reported concerning differences in the pharmacokinetics of CSA and CSG in preclinical studies, and no data exist regarding the effect of steady-state oral administration of CSG on renal function in transplant patients or CSG-induced release of endothelin and nitric oxide (NO) in vivo. The objective of the study was to examine steady-state pharmacokinetic profiles of adult renal allograft recipients receiving CSA and CSG in relation to concentrations of endothelin-1 and NO2/NO3 in urine and plasma, creatinine clearance (Clcr), and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) 9 months after transplantation. Concentrations of CSA and CSG were measured in whole blood over a 12-hour dose interval by both a monoclonal and polyclonal fluorescence polarization radioimmunoassay for CSA. A metabolite fraction was defined as the numerical difference between the levels obtained at each time point by both assays. Patient groups were defined as follows: group 1: initial CSA (n = 6); group 2: initial CSG (n = 7); group 3: five of the seven patients in group 2 taking CSG subsequently undergoing conversion to CSA; group 4: the same five patients in group 3 restudied 1 month after 1:1 dosage conversion to CSA; and group 5: CSA groups 1 and 4 combined (n = 11). In group 1, the metabolite fraction accounted for 32% to 54% of the total measurable drug concentration at each time point, whereas in group 2, the metabolite fraction accounted for at most 10% to 15% of the total drug levels measurable by polyclonal fluorescence polarization radioimmunoassay. Although there were no significant differences in any of the mean pharmacokinetic parameters between groups using monoclonal fluorescence polarization radioimmunoassay, the normalized area under the concentration-time curve (NAUC) value was less in four of five patients after conversion from CSG to CSA, with a more variable and delayed time to reach peak concentration (tmax) but equivalent apparent oral clearance (Clpa) values. Clcr was found to change significantly with time in groups 1 and 5 but not in group 2, with CSA producing a more profound and sustained decrease than CSG. Endothelin-1 and NO2/NO3 levels in plasma and urine remained relatively constant after administration of both CSA and CSG, and there were no significant differences between groups 3 and 4 regarding mean endothelin-1 and NO2/NO3 concentrations in plasma, urinary release of endothelin-1 and NO2/NO3, and mean AUC of endothelin-1 and AUC of NO2/NO3. However, monoclonal NAUC correlated significantly with total urinary endothelin-1 within CSA groups 1 and 5 but not within CSG group 2. Metabolite NAUC correlated significantly with total urinary NAG within CSA group 1. Although limited by the small number of patients, this study suggests that 1) CSG may produce less of a reduction in Clcr over time after oral administration at steady state than does CSA, and 2) this beneficial effect of CSG may be in part due to decreased intrarenal release of endothelin-1, as urinary excretion of endothelin-1 seemed to correlate better with CSA than with CSG exposure.

Objective: To evaluate the efficacy, safety, and cost of preemptive ganciclovir therapy in cytomegalovirus (CMV)-seropositive renal transplant recipients treated with antilymphocyte antibody (ALA) preparations., Design and Setting: A prospective, randomized trial at a 650-bed tertiary medical center hospital., Patients: Forty consecutive CMV-seropositive renal allograft recipients who underwent transplantation between January 1992 and January 1994 and were treated with ALA for induction immunosuppression or acute rejection therapy., Main Outcome Measures: The incidence and severity of CMV disease, length of hospitalization, and patient and allograft survival., Intervention: Cytomegalovirus infection prophylaxis by use of intravenous ganciclovir during ALA therapy was administered to 22 patients (group 1) and the results were compared with those obtained in 18 control patients who did not receive prophylaxis for CMV disease (group 2)., Results: Preemptive ganciclovir therapy significantly reduced the incidence of CMV disease (P < .05) in CMV-seropositive renal transplant patients who were treated with ALA and was well tolerated. In addition, the cost of prophylactic therapy was offset by the decreased length of hospitalization observed in patients in group 1., Conclusion: Preemptive ganciclovir therapy provides a cost-effective approach toward significantly improving the outcome of renal transplantation in CMV-seropositive patients treated with ALA.

Objective: To compare the efficacy, safety, and cost of prophylactic low-dose ganciclovir with that of immunoglobulin in renal transplant recipients at risk for primary cytomegalovirus (CMV) disease., Design and Setting: A prospective, randomized trial at a 650-bed tertiary medical center hospital., Patients: Fifty-one consecutive CMV-seronegative patients who received renal allografts from seropositive donors between March 1990 and April 1992., Main Outcome Measures: Patient and allograft survival, and the incidence and severity of CMV disease., Intervention: Cytomegalovirus prophylaxis with seven doses of intravenous immunoglobulin for 6-week periods (group 1, n = 27) or low-dose intravenous ganciclovir for 3 weeks (group 2, n = 24). Results were compared with those obtained in 23 CMV-seronegative historical controls who received renal allografts from CMV-seropositive donors between 1987 and 1989, and who did not receive prophylaxis for CMV (group 3)., Results: Both prophylactic regimens significantly reduced the incidence of invasive CMV infection (P < .05) and were well tolerated. However, the cost of ganciclovir ($350 per patient) was substantially less than that of immunoglobulin ($4000 per patient)., Conclusions: These data suggest that prophylactic ganciclovir therapy provides a cost-effective approach toward significantly improving the outcome of renal transplantation in recipients at risk for primary CMV disease.

The cephalic vein within the deltopectoral groove provides adequate access to the central venous system for the PermCath hemodialysis catheter. Unlike EJV techniques, which are successful in few instances, the cephalic vein approach was successful in approximately 75 percent of instances. In addition, the rate of complications secondary to bleeding or catheter kinking are decreased with the cephalic vein technique as compared with insertion through the EJV or IJV. We conclude that the cephalic vein is a dependable and functional approach to the central venous system for the PermCath hemodialysis catheter.

AM1 (M17) is the major metabolite of cyclosporine found in the blood of human transplant recipients, and trough levels of this derivative exceed those of the parent compound approximately two-fold. Studies performed in vitro indicate that AM1 retains only 10-20% of the biological activity of the parent compound, but very little is known about its in vivo immunosuppressive effects. We therefore developed a rapid and sensitive method, based on the rejection of allogeneic L1210 (H-2d) leukemia cells by C57BL/6 (H-2b) mice, to assess the immunosuppressive activity of AM1 in vivo. Rejection of the leukemia allograft was determined by analyzing the spleens from mice injected intravenously with 10(5) L1210 cells for the presence of H-2Kd-positive cells by flow cytometry using an FITC-conjugated monoclonal anti-H-2Kd antibody. Nonimmunosuppressed mice rejected the allogeneic cells and survived indefinitely. Spleens from these mice were virtually free of H-2Kd-positive cells (0.51 +/- 0.21%) by day 7. In contrast, C57BL/6 mice treated with 10 mg/kg/day s.c. of CsA all died from the L1210 challenge (mean survival time of 9 +/- 1 days). Spleens from mice treated in this manner contained 11.02 +/- 3.31% H-2Kd-positive cells on day 7. There was a direct correlation between the dose of CsA administered (7.5-50 mg/kg/day) and the percentage of H-2Kd-positive cells in the spleen. We then compared the immunosuppressive activity of AM1 and CsA in this model. AM1 was purified from the urine of CsA-treated renal allograft recipients by a combination of preparative adsorption-desorption chromatography and preparative elution high-performance liquid chromatography. AM1 at a dose of 10 mg/kg/day exhibited no demonstrable immunosuppressive effect, and trough levels of AM1 on day 7 were only 36 +/- 4 ng/ml. Increasing the dose of AM1 to 50 mg/kg/day resulted in only 1.05 +/- 0.16% H-2Kd-positive cells in the spleens (P = NS) and a mean trough level of 221 +/- 27 ng/ml. In contrast, mice treated with 50 mg/kg/day of CsA exhibited 17.7 +/- 2.9% H-2Kd-positive cells in their spleens and a mean trough CsA level of 3036 +/- 277 ng/ml. The half-life of a single subcutaneous dose of 10 mg/kg of AM1 (4.6 hr) was significantly shorter than that of CsA (9.7 hr) in mice. Compared with CsA, the lack of immunosuppressive effect of AM1 in vivo therefore appears to be due to a combination of decreased immunosuppressive activity and increased rate of clearance in mice.

We have evaluated the effects of CsA, methylprednisolone (MP), 6-mercaptopurine (6-MP), and FK506 on T cell-dependent and T cell-independent immunoglobulin production. FK506 and 6-MP were potent inhibitors of IgG and IgM production by PWM-stimulated peripheral blood mononuclear cells, which depend on the presence of T cells. CsA was less effective in this system and MP actually enhanced IgG and IgM production. In order to assess the direct effects of these various immunosuppressive agents on B cells, we utilized human B cell lines representing different stages of B cell differentiation. The B cell lines CESS and SKW6.4 exhibit increased production of IgG and IgM, respectively, in response to interleukin-6. These cells represent activated, but not fully differentiated, B cells. CsA inhibited IL-6-induced IgG production by CESS cells by 64% at 100 ng/ml and 6-MP inhibited this response by 82% at 250 ng/ml. Neither CsA nor 6-MP effectively inhibited IL-6-induced IgM production by SKW6.4 cells. MP at 250 ng/ml inhibited IL-6-induced IgG production by 89%, but enhanced IL-6-induced IgM production more than two-fold. FK506 did not inhibit IL-6-induced IgG or IgM production, suggesting that it has no direct effect on the ability of B cells to respond to this differentiation factor. These experiments clearly demonstrate that CsA, MP and 6-MP have direct inhibitory effects on the response of human B cells to IL-6. In contrast, FK506 has no direct effect on these B cells lines, but is more potent than the other agents at inhibiting T cell-dependent immunoglobulin production.

The immunosuppressive properties of polar and nonpolar maleimides were studied by measuring their ability to inhibit mitogen-induced interleukin-2 (IL-2) production by JURKAT T cells. The nonpolar maleimides N-ethylmaleimide (NEM) and N-phenylmaleimide (NPM) inhibited IL-2 production by 85-99%, but only when added to JURKAT cells prior to the mitogen. The polar maleimides N-hydroxymaleimide (NHM) and 4-maleimidosalicylic acid (M84) did not suppress IL-2 production significantly, even though NHM reacted with more cellular thiols (12%) than did NPM (8%). Both NEM and NPM suppressed IL-2 production at doses that did not affect proliferation. NEM inhibited IL-2 production induced by PHA, anti-CD3 (alpha CD3) monoclonal antibodies or PMA, and A23187, but did not interfere with the binding of alpha CD3 to the cells. NEM inhibited IL-2 production at concentrations that did not interfere with the PHA-induced increase in intracellular free calcium [( Ca]i). Neither NPM nor NHM inhibited the rise in [Ca]i, even at the highest concentrations tested. Although JURKAT T cells require both PMA and A23187 to induce IL-2 production, we found that cells pretreated with PMA could respond to A23187 added 18 hr later. PMA-treated cells were not resistant to the immunosuppressive effects of NEM or NPM. However, PMA-pretreated cells became resistant to the inhibitory effects of NEM upon the addition of A23187, suggesting that nonpolar maleimides inhibit activation events induced by the rise in [Ca]i.

The thiol-alkylating agent, N-ethylmaleimide (NEM), was found to inhibit the response of human peripheral blood mononuclear cells to the T-cell mitogen, concanavalin A (Con A). NEM (10 microM) blocked Con A-induced agglutination, production of interleukin-2 (IL-2) and expression of the IL-2 receptors (Tac) without toxicity. In order to determine whether the effects of NEM on lymphokine production were related to inhibition of agglutination, we compared the immunosuppressive effects of NEM with those of cytochalasin A, cytochalasin B and colchicine. NEM did not inhibit E-rosette (ER) formation, suggesting that it does not interfere with actin filaments. Low concentrations of NEM (4 microM) inhibited IL-2 production and Tac expression without inhibiting agglutination, while 6-10 microM NEM blocked agglutination and DNA synthesis as well. In contrast, 5-10 microM cytochalasin B (CB) inhibited ER formation, agglutination, Tac expression and DNA synthesis, but augmented IL-2 production by three- to ten-fold. Colchicine (0.1-10 microM) had no effect on ER formation or agglutination and augmented IL-2 production by as much as 18-fold. However, colchicine blocked Tac expression by greater than 40% and DNA synthesis by greater than 80%. Cytochalasin A (CA), which has the thiol-reactive properties of NEM, the actin filament-disrupting properties of CB, and the microtubule-disrupting properties of colchicine, exhibited the immunosuppressive effects of all three compounds. These studies suggest that the inhibitory effects of NEM on IL-2 production do not appear to be due to reactivity with the cytoskeleton, but are probably due to effects on signal transduction pathways leading to IL-2 production and expression of IL-2 receptors.

The use of immunosuppressive therapy has markedly increased over the past several years, and concomitant with its use has been an increased frequency of associated neoplasia. The patient presented is a 22-year-old white male who, following two renal transplants and prolonged immunosuppressive therapy with azathioprine and methylprednisolone, developed chronic granulocytic leukemia. Chromosome karyotyping demonstrated the somewhat unusual development of a Philadelphia chromosome with translocation to the No. 7 of the C group. A review of transplantation centers revealed that five cases of chronic granulocytic leukemia have occurred in a population of 25,000 renal transplant patients, a 5-fold increased incidence over the general population. Possible etiologies that may be responsible for the development of chronic granulocytic leukemia in patients on immunosuppressive therapy are discussed. It is our hope that by the introduction of these reports of chronic granulocytic leukemia into the medical literature, the need for caution in the use of immunosuppressive drugs in nonmalignant disease will again be emphasized.

Cellular thiols are known to be involved in lymphocyte activation, differentiation, and growth. In theory, alkylation of selective cellular thiols could be used to regulate specific processes in the activation sequence by inactivating particular enzymes or structural proteins, although to date specific alkylating probes have not been reported. N-Ethylmaleimide (NEM) is a lipophilic sulfhydryl-alkylating agent that is known to block the in vitro proliferative response of T lymphocytes. NEM (10 microM) was found to be fully inhibitory in PHA, Con A, and MLC assays only when added prior to or simultaneously with the mitogens or allogeneic cells; the addition of NEM only 15 sec after stimulating the cells with PHA resulted in a loss of greater than 50% of the inhibitory activity. The addition of 50 microM 2-ME 10 min after treating the cells with NEM failed to block the inhibitory effect. NEM (10-20 microM) had no adverse effect on lymphocyte viability, but completely blocked lymphocyte agglutination in response to mitogens or allogeneic cells. The lymphocytes overcame the inhibitory effects of NEM after 48 hr in both the PHA and MLC experiments. Resumption of the proliferative response was associated with the onset of agglutination in the PHA assay. In experiments using various analogs of NEM, we noted that the presence of a nonpolar N-linked side group was necessary for inhibitory activity. Pretreatment of PBMC with NEM decreased the total cellular thiols by 50% and blocked proliferation by 99%, whereas N-hydroxymaleimide decreased the total cellular thiols by 38% but had no effect on the proliferative response. The additional 12% of the cellular thiols that react with NEM, but not NHM, account for the inhibitory effect of NEM on lymphocyte proliferation. These findings suggest that selective cellular thiols are critical for T-cell activation.

Hydrogen peroxide, a reactive oxygen intermediate produced by activated neutrophils, has been shown to inhibit the response of human T lymphocytes to mitogens and alloantigens. Since hydrogen peroxide is known to react with iron and to induce lipid peroxidation, we compared the effects of hydrogen peroxide and a lipid peroxidation product, malondialdehyde, on the response of human peripheral blood mononuclear cells to T-cell mitogens. Peripheral blood mononuclear cells pretreated with 1 mmol/L of malondialdehyde, washed, and resuspended in fresh medium exhibited no inhibition of phytohemagglutinin responsiveness. Peripheral blood mononuclear cells treated in the same manner but with 200 mumol/L of hydrogen peroxide were inhibited by more than 95%. The addition of ferric edetate did not alter the inhibitory effects of 50 to 100 mumol/L of hydrogen peroxide, nor did the addition of deferoxamine, an iron chelator. These studies suggest that exogenous lipid peroxidation does not affect lymphocyte activation but that hydrogen peroxide has a direct inhibitory effect. Although monocytes are necessary for T-cell mitogenic responses, the effect of hydrogen peroxide was found to be directed at T lymphocytes. Exposure of T cells to a single dose of 200 mumol/L of hydrogen peroxide resulted in more than 71% suppression of the proliferative response measured 48 hours later, but the effect was spontaneously reversed by 72 to 96 hours. Repeated exposure of the cells to hydrogen peroxide resulted in continued inhibition of the proliferative response. These findings suggest that hydrogen peroxide produced by inflammatory phagocytic cells might be capable of suppressing the immune response of nearby T lymphocytes.

Hydrogen peroxide (100 to 200 microM) inhibited the response of human peripheral-blood mononuclear cells (PBMCs) in phytohemagglutinin, concanavalin A, and mixed lymphocyte culture assays by more than 90% without affecting cell viability. The response of PBMCs to pokeweed mitogen was stimulated twofold by 50 microM H2O2, but 200 microM H2O2 inhibited the pokeweed mitogen response by more than 95%. A 50 microM concentration of H2O2 completely blocked the generation of cytotoxic T cells in the mixed lymphocyte culture but did not inhibit the production of interleukin 2. Concentrations of 100 microM to 200 microM H2O2 inhibited interleukin 2 production by 45% to 57%. The H2O2 appeared to block early events in T-cell activation, since 200 microM H2O2 was not inhibitory when added one hour after stimulating the cells with phytohemagglutinin. Treatment of PBMCs with 200 microM H2O2 did not decrease the total cellular thiol pool, suggesting that H2O2-mediated inhibition of the proliferative response was not due to thiol oxidation. However, pretreatment of PBMCs with the lipid antioxidants butylated hydroxyanisole, butylated hydroxytoluene, and n-propyl gallate blocked more than 75% of the inhibitory effect of H2O2, suggesting that H2O2 inhibits T-cell activation by inducing lipid peroxidation.