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Background Clinical and laboratory criteria are not reliable predictors of deceased donor liver graft quality. Intraoperative assessment of experienced surgeons is the gold standard. Standardizing and quantifying this assessment is especially needed now that regional sharing is the rule. We prospectively evaluated a novel, simple, rapid, noninvasive, quantitative measure of liver function performed before graft procurement. Materials and methods Using a portable, finger-probe-based device, indocyanine green plasma disappearance rates (ICG-PDR) were measured in adult brain-dead donors in the local donor service area before organ procurement. Results were compared with graft function and outcomes. Both donor and recipient teams were blinded to ICG-PDR measurements. Results Measurements were performed on 53 consecutive donors. Eleven liver grafts were declined by all centers because of quality; the other 42 grafts were transplanted. Logistic regression analysis showed ICG-PDR to be the only donor variable to be significantly associated with 7-d graft survival. Donor risk index, donor age, and transaminase levels at peak or procurement were not significantly associated with 7-d graft survival. Conclusions We report the successful use of a portable quantitative means of measuring liver function and its association with graft survival. These data warrant further exploration in a variety of settings to evaluate acceptable values for donated liver grafts.

Background: Frailty has been implicated as a negative predictor of Liver Transplant (LT) outcomes. However, an understanding of changes in patient muscle mass peri-LT, and their effect in high-acuity patients remains lacking. We examined the impact of perioperative muscle mass changes (ΔSMI) on high-acuity (MELD ≥35) LT recipients., Materials and Methods: Skeletal muscle index (SMI) was calculated using CT imaging. Patients were divided into two groups, based on severity of peri-operative SMI decrease. LT recipients with chronic end-stage liver disease, MELD ≥35, and abdominal CT ≤30 days prior, and 30-90 days post LT were included. [1011 adult LT recipients reviewed, 2012-2018]., Results: Of 1011 patients reviewed, 88 met inclusion criteria (median MELD 41.1). The median ΔSMI was -5.0 (-29.4 - +21.1 cm 2 /m 2 ) (fig A). Patients were classified into two groups: ΔSMI<-5.0 (median ΔSMI: -0.4, n = 44) and ΔSMI>-5.0 (median ΔSMI: -9.2, n = 44). Recipients with ΔSMI<-5.0 had higher pre-LT SMI (35.4 versus 31.2 cm 2 /m 2 , P <0.001) and lower post-LT SMI (26.0 versus 30.8 cm 2 /m 2 , P <0.001). The ΔSMI<-5.0 group had higher early allograft dysfunction (40.9 versus 20.5%, P = 0.037), and inferior patient and graft survival (P = 0.015, 0.017, respectively). Multivariate analysis identified ΔSMI<-5.0 (HR: 2.938, P = 0.048), long cold-ischemia time (≥9h, HR: 7.332, P = 0.008), HCV (HR: 5.614, p = 0.001), and tracheostomy after LT (HR:9.218, P <0.001) as negative prognostic factors for patient survival ., Conclusions: Progressive perioperative sarcopenic deterioration was associated with inferior patient and graft survival in high acuity LT. These findings may guide pre and post-operative patient care and rehabilitation efforts in this challenging patient population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: It is not uncommon for liver transplant (LT) recipients to have had previous abdominal surgery (PAS) preceding transplant. The impact of PAS on morbidity and mortality in LT patients remains unclear. In this study, we investigated the correlation between PAS and LT outcomes in a high-acuity patient population., Materials and Methods: This is a single-center retrospective review of 936 adult primary LT recipients between 2012 and 2018. Patients were divided based on PAS history. PAS was subdivided into upper abdominal surgery (UAS) and lower abdominal surgery (LAS). UAS was separated into high-impact UAS and low-impact UAS. Finally, we studied patients with PAS ≤90 d versus PAS >90 d., Results: Extensive adhesiolysis was the only significant perioperative factor between the PAS group (n = 367) and the non-PAS group (n = 569) (P < 0.001). Red blood cell (RBC) transfusion (20U versus 17U, P = 0.044) and abdominal packing (24.2% versus 13.3%, P = 0.008) were significantly higher in the UAS group (n = 186) versus the LAS group (n = 181). Patients with high-impact UAS required greater RBC (P = 0.021) and fresh frozen plasma transfusion (P = 0.005), and arterial conduits (P = 0.016) during LT. Compared with recipients with PAS >90 d (n = 338), recipients with PAS ≤90 d (n = 29) had significantly higher RBC transfusion (P = 0.046), fresh frozen plasma transfusion (P = 0.022), and abdominal packing (P = 0.025). No differences in patient and graft survival was observed., Conclusions: These findings suggest that, with appropriate care in the perioperative setting, PAS is not a contraindication to successful LT. Careful consideration is warranted when risk stratifying patients with multiple comorbidities who had PAS, especially those with UAS or PAS ≤90 d., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Gene therapy represents a promising treatment for hepatic disease. Most approaches today use viral methods to target tissues. While nonviral gene therapy is less prominent, hydrodynamic gene delivery represents a promising approach to direct gene expression to the liver. The purpose of the present study was to evaluate promoters for efficient gene expression in hepatocytes in vivo by hydrodynamic delivery and to test the findings in a model of hemophilia A., Materials and Methods: Human cytomegalovirus (hCMV), chicken beta-actin/CMV enhancer (CAG), elongation factor-1 alpha (EF1alpha), and phosphoglycerokinase (PGK) promoters were subcloned into plasmids with a luciferase reporter gene. In vitro calcium phosphate-mediated transfection of 2 x 10(5) HEK 293 cells was followed by in vivo whole animal bioluminescence and luminometry after hydrodynamic tail vein injection of plasmid DNA. Six-month-old FVB factor VIII (FVIII)-deficient mice were similarly injected with CBA- or EF1alpha-promoted constructs containing the FVIII heavy and light chains and expression was examined., Results: In vitro transfection demonstrated a hierarchy of expression: hCMV-intron>CAG>EF1alpha>hCMV>>PGK. In vivo luminometry demonstrated that the CAG construct produced 2.6x, 3.0x, 3.4x, and >1000x the expression of the hCMV-intron, EF1alpha, hCMV, and PGK constructs respectively. FVIII plasmid injected hemophilic mice demonstrated higher levels of FVIII expression with CAG versus EF1alpha, confirming the reporter gene studies. All FVIII-deficient mice injected with EF1alpha-FVIII or CAG-FVIII plasmids survived after tail clipping., Conclusions: The CAG promoter/enhancer combination is an excellent alternative to the human CMV promoter for hydrodynamic gene delivery to the liver.

Background: We have previously shown that >75% of LEW cardiac allografts survive indefinitely in BUF rats pretreated at Day -21 intrathymically (IT) with donor alloantigen in conjunction with a single intravenous dose of ALS. Spleen cells can adoptively transfer the tolerant state to new cohorts of test recipients. This study was designed to analyze cellular and humoral events contributing to the "infectious" tolerance pathway in this model., Methods: Spleen cells (25 x 10(6)) harvested from BUF recipients bearing long-term cardiac allografts were injected intravenously into lightly irradiated (450 R) secondary BUF rats, followed 24 h later by transplantation of LEW of ACl hearts. Cardiac allografts were then analyzed serially by reverse transcription polymerase chain reaction for Th1 and Th2 cytokine gene expression. Donor-specific IgM and IgG alloantibody responses in host serum were screened by flow cytometry., Results: Transfer of regulatory spleen cells harvested between Days 80 and 140 from tolerant hosts induced tolerance to heart grafts in a donor-specific manner. In the early posttransplant period, selective sparing of Th2 cytokines was noted. Adoptively transferred hosts showed overall depression of IgM, but a vigorous IgG1 and IgG2a alloantibody response., Conclusion: IT + ALS-induced tolerance can be transferred in a donor-specific "infectious" manner to new cohorts of engrafted recipients. The development of tolerance is nontemporally bound, and associates with an early Th2-type immune deviation at the graft site. The elevated levels of T cell-dependent IgG1 and IgG2 may interfere with the antigen reactivity and alloresponsive effector functions, contributing to graft acceptance in the "infectious" tolerance pathway., (Copyright 1999 Academic Press.)

Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been shown to decrease the number of acute rejection episodes in cardiac and renal transplant patients. This study evaluates the effects of pravastatin on survival of rats following liver transplant and attempts to elucidate the mechanisms of these effects. Both survival and natural killer cell enhancing factor (NKEF) studies utilized Dark Agouti rats for donor livers transplanted into Brown Norway rats as recipients. All rats received daily low-dose cyclosporine (CsA) 2 mg/kg/day by gavage. The treated groups also received gavage doses of pravastatin, 20 mg/kg/day. Survival data were analyzed by the method of Kaplan-Meier and log-rank chi 2 tests for statistical significance. For NKEF evaluation, rats were sacrificed at varying time points; total RNA was extracted from the liver and hybridized with 32P-radiolabeled NKEF DNA probes in the Northern blot technique. Radiographs were quantitated using densitometry. Data were analyzed by two-way ANOVA. Actuarial survival was improved (P < < 0.05) in rats treated with pravastatin in addition to low-dose CsA (n = 41, CsA alone n = 74). Less fibrosis and chronic rejection was seen on histological section in the treated animal livers, P < 0.05, NKEF was seen maximally at Days 5-15 tapering off at Day 21. NKEF-a and NKEF-b levels were significantly decreased in the animals treated with CsA and pravastatin compared to CsA alone in the group of animals < 16 days postop (P < < 0.05). Pravastatin improves survival in rats following OLT and while the mechanism is still unknown, inhibition of natural killer cell enhancement factor may represent an alteration in the overall immune response.

Inherited and acquired disorders of the liver are attractive targets for gene therapy. Hepatic cells are susceptible targets for shuttle vectors because of a diversity of protein and viral receptors and accessibility of a selective afferent blood supply. Preservation of existing hepatic cell integrity and metabolic function is of paramount importance for successful whole animal gene therapy trials. In this report, we examine hepatic cell function and integrity following adenovirus-mediated reporter gene transfer to the liver in vivo. E1-deleted, replication-defective adenovectors encoding the LacZ gene driven by the human CMV promoter were delivered to the liver by isolated portal perfusion. The gene transfer rate, as determined by specific histochemical staining, approached 30% with recombinant protein detectable by Western blot throughout the course of study. Hepatic cell integrity as assessed by histology and hepatic enzyme profile (serum aspartate aminotransferase, gamma-glutamyl transpeptidase) demonstrated normal cellular architecture and no significant difference between transfected liver and controls. Hepatic synthetic and metabolic function, as determined by albumin levels, prothrombin time, and bilirubin, were similar between the two study groups. This study demonstrates that efficient adenovirus-mediated gene transfer and expression in the rat liver do not compromise hepatic cell metabolism and integrity.

The application of gene therapy in transplantation might be targeted at immunoregulation within the donor graft. Viral IL-10 (vIL-10) down-regulates antigen presenting cells (APC) and effector functions in in vitro and in vivo models of alloreactivity. In the current study, we have constructed a replication-defective adenovirus bearing the cDNA encoding viral IL-10 and examined the level and chronicity of its expression in rat liver allografts up to 7 days after orthotopic transplantation. The results demonstrate that liver allografts may be efficiently transfected with adenovirus expressing viral IL-10. Detection of the recombinant viral cytokine was limited to the allograft without measurable levels in peripheral blood. In parallel, the effect of vIL-10 on mixed leukocyte reaction is also assessed using peripheral blood lymphocytes obtained from naive donor and recipient animals. Equivalent levels of viral IL-10 (5-10 ng/ml) achieved after adenovirus-mediated gene transfer suppress the in vitro alloreactivity of peripheral blood lymphocytes up to 70%. Adenovirus-mediated gene transfer of viral IL-10 offers the promise of effectively and favorably altering the alloreactive immune response.

Interleukin-1 receptor antagonist (IL-1ra) competes with IL-1 for binding of the IL-1 receptor, but does not elicit a cellular immune response. This study was designed to evaluate the effectiveness of IL-1ra in the immune and inflammatory responses to rat heart allografts. Experimental design was as follows: Group I HTx was syngeneic, BN to BN. The remaining groups were DA (RT 1a) to BN (RT 1n) allogeneic HTx. Group II was transplanted without immunosuppression. Group III received a low-dose IL-1ra regimen via osmotic pump into the peritoneum. Group IV recipients were similarly treated with a higher dose IL-1ra regimen. Group V rats received subtherapeutic cyclosporine (CsA) therapy while Group VI was treated with both CsA and low-dose IL-1ra. Group I rats survived indefinitely. Group II rats rejected their grafts at 5.33 +/- 1.37 days. Group III grafts survived for 7.16 +/- 0.48 days, and Group IV grafts for 8.16 +/- 0.75 days, both significantly longer than in Group II (P < 0.01). Group V animals treated with low-dose CsA had graft survival of 7.7 +/- 1.6 days, but combined therapy with CsA and IL-1ra in Group VI yielded significantly prolonged graft survival of 17.2 +/- 1.3 days (P < 0.0001). Histologic examination in treated recipients revealed delayed appearance of mononuclear cell infiltration. IL-1ra-treated recipients all demonstrated significantly reduced numbers of graft-infiltrating leukocytes; all phenotype subsets were equally affected. This study demonstrates the effectiveness of IL-1ra, in combination with low-dose CsA, in reducing the inflammatory response and rejection in the transplant setting.

Detection of rejection after small intestine transplantation (SIT) is difficult, relying largely on histopathology. The purpose of this study was to determine if the intragraft expression of messenger RNA (mRNA) for interleukin-2 receptor (IL-2R), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF) correlated with rejection in a unidirectional, heterotopic rat SIT model. Graft samples were obtained on postoperative day (POD) 3, 5, 7, 8, 9, 10, 12, and 14. After staining, formalin-fixed samples were blindly evaluated for rejection. Reverse transcriptase polymerase chain reaction (rtPCR) using primers specific for beta-actin, IL-2R, IL-6, and TNF was performed on liquid nitrogen-frozen samples. Semiquantitation was accomplished using radionuclide incorporation and beta-scintillation counting. Intestinal histopathology in all isografts (ISO) and POD 3 allografts (ALLO) was normal. Rejection progressed in ALLO from mild on POD 5 to severe by POD 8. rtPCR analysis revealed constitutive expression of IL-2R mRNA in both ISO and ALLO. TNF and IL-6 demonstrated significant increases in mRNA expression in ALLO compared to ISO beginning on POD 5. In summary, intragraft expression of IL-2R mRNA demonstrated late up-regulation in ALLO which did not correlate with rejection. TNF and IL-6 mRNA expression predicted rat SIT rejection. rtPCR analysis of TNF and IL-6 may serve as a useful diagnostic adjunct for rat SIT rejection.

Unlabelled: The arterial ketone blood ratio (AKBR) of acetoacetate to b-hydroxybutyrate was previously shown to reflect hepatic mitochondria oxidation/reduction (redox) state and energy level. In this study we correlated AKBR to the degree of liver injury immediately following orthotopic liver transplantation (OLT). Serial measurements of AKBR in 209 patients undergoing OLT, during the anhepatic phase, and up to 60 hr following reperfusion demonstrated direct correlation between mitochondria Redox state (AKBR), hepatocyte injury (SGOT), and hepatic synthetic function (prothrombin time). AKBR levels less than 0.7 were seen in primary nonfunction grafts and were associated with raising SGOT (greater than 1000) and prolonged PT (greater than 18). Acute occlusion of arterial blood supply to the graft was seen in conjunction with low AKBR (less than 0.7). However, hepatic synthetic function and serum enzyme were stabilized or returned to normal within 24-48 hr postreperfusion., In Conclusion: (1) AKBR measurements are useful in predicting graft survival, (2) reduction in liver mitochondria Redox state is seen in primary hepatocyte dysfunction and correlates well to synthetic function, and (3) acute occlusion of the arterial supply to the liver graft is associated with decreased redox state. However, with intact portal blood flow, it is still possible to preserve adequate hepatic synthetic function.

Prostaglandins of the E series have been shown to decrease renal and hepatic ischemic injury as well as improve hepatic function in patients with primary nonfunction following transplantation. We wished to determine the effect of prostaglandin E1 (PGE1) on hepatic allograft reperfusion injury in the isolated perfused rat liver (IPRL) model. Livers were harvested from adult male Sprague-Dawley rats and the bile duct, portal vein, and suprahepatic vena cava were cannulated. Control livers were placed immediately on the IPRL apparatus and perfused for 2 hr with a blood-Kreb's solution. Group A and B allografts were stored for 8 hr in heparinized lactated Ringer's solution at 4 degrees C. Group A livers were then perfused with a PGE1 infusion at 0.1 micrograms/kg/min while B livers received a placebo infusion of NS at the same rate. Temperature, pH, and inflow pressures were kept constant. Oxygen consumption, portal flow, and resistance were calculated for each group and found not to be statistically different. LDH, SGOT, superoxide anion (SOA), and bile flow were measured at 30-min intervals. At the end of the 2-hr perfusion, the placebo Group B (N = 5) had LDH, SGOT, and SOA higher than those of either Group A (N = 5) or control (N = 4) livers. The difference between Group A and Group B was significant for SGOT and SOA (P less than 0.05). Bile flow was highest in the control group (24.2 +/- 1.8 microliters/g/30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor necrosis factor (TNF) levels have been reported to be elevated during episodes of human renal, hepatic, and cardiac transplant rejection. In addition, we have shown polyclonal anti-TNF antibodies to have immunosuppressive effects. The present study was performed to evaluate the efficacy of a monoclonal anti-TNF-alpha antibody in rat cardiac transplantation as the sole immunosuppressant and in conjunction with low-dose cyclosporine (CsA). We also performed immunohistological studies to localize intragraft TNF and evaluate graft infiltrating cells (GICs), and we measured serum TNF levels by an ELISA. Untreated Buffalo to Lewis heterotopic rat cardiac transplants reject in 10.5 +/- 0.4 days. A 10-day induction course of CsA (2 mg/kg/day, po) prolonged survival to 16.7 +/- 2.7 days (P less than 0.05 vs control), and 10 days of anti-TNF (2000 U/day, ip) prolonged survival to 22.6 +/- 0.8 days (P less than 0.05 vs control). Combination of anti-TNF plus CsA synergistically prolonged graft survival to 40.7 +/- 1.8 days. Three-day courses of anti-TNF were moderately effective (13.7 +/- 0.5 days, P less than 0.05 vs control) and were also synergistic with CsA (27.8 +/- 2.2). Intragraft TNF localization using immunoperoxidase showed extensive perivascular and mononuclear cell staining in control hearts vs minimal staining in anti-TNF-treated groups. Likewise, serum TNF levels were significantly lowered for treated groups vs control (83.1 +/- 14.0 pg/ml for control; 39.5 +/- 13.8 for anti-TNF; and 13.4 +/- 5.4 for anti-TNF + CsA; P less than 0.05 vs control for all groups).(ABSTRACT TRUNCATED AT 250 WORDS)

We have recently observed significantly elevated serum tumor necrosis factor-alpha (TNF-alpha) levels during human liver allograft rejection. Although increased TNF activity has been reported in rejecting rat cardiac and renal allografts, this represents the first report of an animal model utilizing immunotherapy directed against TNF. Intraabdominal heart transplants (Buffalo to Lewis) were performed. Cardiac rejection was defined as cessation of a palpable beat and confirmed at laparotomy. Control animals received no immunotherapy and experienced rejection on Postoperative Day 11 +/- 0.4 (mean +/- SEM). Experimental animals received immunotherapy either intraperitoneally (ip) or intravenously (iv) from Days 1 to 10. Intraperitoneally administered anti-TNF-alpha prolonged graft survival to 16 +/- 2.7 days (P less than 0.05 vs controls), iv administration prolonged survival to 15 +/- 1.4 days (P less than 0.004). Animals treated with ip anti-TNF-beta survived 17 +/- 1.7 days (P less than 0.002 vs controls). Conversely, administration of purified TNF-alpha to graft recipients decreased graft survival to 7 +/- 0.4 days (P less than 0.001 vs controls). Serum samples analyzed in an L929 bioassay showed increased cytotoxic activity in control animals, corresponding to an increase in circulating TNF. This activity was partially abrogated in animals receiving immunotherapy. These data demonstrate that circulating levels of TNF are increased during rejection. Immunotherapy with anti-TNF-alpha or anti-TNF-beta prolongs graft survival, suggesting that TNF may play a role in the pathogenesis of acute allograft rejection.

Antibiotics play an important role in helping the host fight infection; however, the direct cellular effect of antibiotics on polymorphonuclear cells remains undefined. Adherence, chemotaxis, phagocytosis, and superoxide anion production are important steps in the cascade of events initiated by the polymorphonucleocyte in bacterial killing. Previous studies have shown inhibition as well as stimulation of neutrophil antibacterial therapy by antibiotics. Peritoneal and blood polymorphonuclear neutrophils (PMN) respond differently to peritonitis and to external agents. The purpose of this study was to investigate the effects of in vivo clindamycin and netilmicin on infected rabbit peritoneal and blood polymorphonuclear adhesiveness, phagocytosis, chemotaxis, and superoxide anion production. Peritoneal and blood PMNs were obtained from rabbits which had undergone appendiceal devascularization 18 hr earlier: antibiotics were administered intramuscularly 1 hr prior to appendectomy and every 8 hr postoperatively for 5 days; these PMNs were compared to infected rabbits which did not receive antibiotics. Clindamycin and netilmicin in vivo cause significant inhibition of phagocytosis, peritoneal adhesiveness, and, when used in combination, blood adhesiveness and peritoneal superoxide anion production. No effects were seen on chemotaxis. Based on this data we conclude that antibiotics, while vitally important in fighting infections, may in and of themselves be agents of immunosuppression at the cellular level.

The neutrophil (polymorphonuclear cell, or PMN) function is an essential component of the host defense against infection. However, infection itself may alter PMN activity. To investigate both the effects of infection on PMN activity and PMN activity on survival, we evaluated control and infected blood and peritoneal PMN phagocytosis, chemotaxis, and superoxide anion production in rabbits with and without peritonitis. Control blood and peritoneal PMNs were obtained from noninfected rabbits which were subjected to intraperitoneal infusion of sterile hypertonic saline. Infected blood and peritoneal PMNs were obtained from rabbits which had undergone appendiceal devascularization and ligation 18 hr earlier. Phagocytosis was similar in all groups except for a threefold increase in normal peritoneal PMNs. Chemotaxis was inhibited by infection in the blood and peritoneal PMNs. Normal peritoneal PMNs also had decreased chemotaxis. Superoxide anion production was comparable in the infected and control blood; however, both control and infected peritoneal PMNs had elevated superoxide anion production. Of the infected rabbits, four died in 5 days or less. Of the six that lived, two developed intraabdominal abscesses. Blood and peritoneal PMN activity was similar in all rabbits despite their outcome. We conclude that (1) blood and peritoneal PMNs have different basal activities and responses to infection; (2) the milieu of the peritoneal cavity appears to alter the PMNs present; and (3) PMN activity did not predict morbidity or mortality.

Neutrophil (PMN) adherence is an important first step in PMN migration. Peritoneal fluid and hemoglobin have been implicated as inhibitors of blood PMN function. The purpose of this study was to evaluate the effects of peritoneal fluid and hemoglobin on PMN adherence in both blood and peritoneal PMNs. Adherence was measured by nylon fiber filtration. Control blood PMNs were obtained from rabbit heparinized blood. Control peritoneal PMNs were obtained by saline lavage 18 hr after the intraperitoneal instillation of hypertonic saline. Infected blood and peritoneal PMNs were similarly obtained from rabbits which had undergone appendiceal devascularization 18 hr earlier. Blood and peritoneal PMNs were tested in normal saline, serum, hemoglobin, and peritoneal fluid from infected and noninfected rabbits. Cell adhesiveness of blood and peritoneal neutrophils from infected and noninfected rabbits was similar in all groups. In normal saline and serum, cell adhesiveness was approximately 70%. In hemoglobin and peritoneal fluid, all groups of neutrophils showed a statistically significant decrease in cell adhesiveness. Based on these data we conclude: (1) Blood and peritoneal PMNs with and without infection have similar adherence. (2) Both hemoglobin and peritoneal fluid inhibit PMN adherence.

Neutrophils play an essential role in the host's defense against infection. Our previous studies have shown that blood and peritoneal neutrophils (PMN) have different basal activities and responses to infection. We also demonstrated that peritonitis produces divergent changes in the cellular function of PMN both in the blood and in the peritoneal fluid. Steroids are well documented to cause immunosuppression both clinically and, more variably, at the cellular level. Understanding the mechanism of steroid-induced immunosuppression in surgical infection may impart insight on the management of this condition. Using a model of surgical peritonitis, we studied the effects of immunosuppression on rabbit blood and peritoneal PMN. Blood and peritoneal PMNs were harvested after the development of fibrinopurulent peritonitis. Rabbits were divided into two groups: immunosuppressed and control. Immunosuppression was accomplished by intramuscular injection of dexamethasone (2 mg/kg) for 10 days preoperatively and 10 days postoperatively. Purified PMNs were studied for phagocytosis, adhesiveness, superoxide anion production and chemotaxis from both groups. Survival was computed from the number of days the rabbit survived after the operation up to a total of 10 at which time they were sacrificed. Immunosuppression with dexamethasone resulted in inhibition of peritoneal phagocytosis and peritoneal adhesiveness; there were no changes in blood adhesiveness nor blood phagocytosis. Also, there was no significant change in superoxide anion production nor in chemotaxis. Survival of the rabbits was significantly reduced when treated with dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)