Urinary trypsin inhibitor concentration can predict the immunological insult of chemotherapy and complications after bone marrow transplantation

Abstract

Summary:Urinary trypsin inhibitor has attracted attention as an index of the systemic inflammatory response syndrome. In this study, the urine concentration of trypsin inhibitor was measured to compare the immunological insult of conventional chemotherapy and conditioning chemotherapy for bone marrow transplantation. We also investigated whether urinary trypsin inhibitor was a useful index of the complications and outcome of bone marrow transplantation. Urinary trypsin inhibitor concentration was determined before chemotherapy, on the day after finishing chemotherapy (day 0 of transplantation), and during recovery of the white cell count, in 17 patients ( seven receiving conventional chemotherapy and 10 receiving conditioning for bone marrow transplantation). Urinary trypsin inhibitor concentrations were significantly higher after conditioning for bone marrow transplantation than after conventional chemotherapy (P Ͻ 0.001), indicating that conditioning was more invasive. After bone marrow transplantation, the incidence of severe complications and the mortality rate were higher in patients whose urinary trypsin inhibitor concentrations rose during recovery of the white cell count. Comparison of urinary trypsin inhibitor concentrations suggested that conditioning for bone marrow transplantation was more invasive than conventional chemotherapy. This study also suggested that the urine concentration of trypsin inhibitor could be useful for predicting the risk of complications and outcome of bone marrow transplantation. Bone Marrow Transplantation (2001) 27, 195-199. Keywords: allogeneic bone marrow transplantation; systemic inflammatory response syndrome; urinary trypsin inhibitor; interleukin-6; C-reactive protein Bone marrow transplantation (BMT) is not only an established therapy for hematological malignancies, but also for Recently, we investigated the relationship between cytokines and vascular endothelial cell dysfunction after BMT and advocated the concept that complications of BMT are collectively caused by the systemic inflammatory response syndrome (SIRS).1-5 The urine concentration of trypsin inhibitor (TI) is known to be very closely associated with the extent of surgical invasion and also reflects the severity of SIRS. 6 In the present study, the usefulness of urinary TI as a predictor of complications and the outcome of BMT was assessed by measuring the concentrations of this marker before and after transplantation. Materials and methods SubjectsThe subjects were 10 consecutive patients who underwent allogeneic BMT from March 1999 to December 1999 and seven consecutive patients who were treated by conventional chemotherapy from September 1999 to December 1999, at our institution. Tables 1 and 2 show the age, gender, underlying disease, and disease stage. These also show the donor, conditioning regimen, and GVHD prophylaxis for BMT patients, as well as the chemotherapy regimen for those given conventional chemotherapy. The basic conditioning regimen was busulfan (BU), cyclophosphamide (CY), and total bo...

Increased serum concentration of urinary trypsin inhibitor with asthma exacerbation

“…In BAL fluid of asthmatic subjects, excessive secretion of proteinases, including NE and MMPs, has been observed during acute asthma exacerbation [12,19]. However, it is hard to detect elevated NE levels in blood, because NE is quickly inactivated and complexed to a 1 antitrypsin in vivo [14,15]. This may explain why the authors were unable to find any difference in the serum levels of NE or a 1 antitrypsin of patients and controls.…”

“…If this is the case, it is not likely that their elevation in serum is detectable. Compared to these proteins, UTI appear to be more stable, because the activity of this protein is detectable in serum or urine [14,15].…”

“…This may explain why the authors were unable to find any difference in the serum levels of NE or a 1 antitrypsin of patients and controls. Several proteins are known to inactivate NE activity and NE degrades the pre-a-/inter-a-trypsin inhibitors, proteinase inhibitors, that release UTI [14,15]. UTI has been reported to be a positive acute phase protein whose concentration in serum and excretion in urine is increased in proportion to the invasiveness of the various diseases and the activation of neutrophils [17,18].…”

“…Assay of urinary trypsin inhibitor, neutrophil elastase, a 1 -antitrypsin, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-2 Serum UTI was determined by sandwich-type one-step enzyme immunoassay using polyclonal antibodies to human trypsin inhibitor [14,17,18] and a human assay kit (Mochida Pharmaceutical Co. Ltd., Tokyo, Japan). The ELISA procedure makes it possible to specifically measure UTI by trapping pre-a-/inter-a-inhibitors in solid phase with a treatment of perchloric acid.…”

“…NE is quickly inactivated by a 1 -antitrypsin, a 2 macroglobulin, pre-a-/inter-a-trypsin inhibitors and anti-leukoprotease in vivo [12,13]. During this process, NE degrades pre-a-/inter-a-trypsin inhibitors to liberate urinary trypsin inhibitor (UTI), which is detectable not only in serum but also in urine [14,15]. The relationship between NE and pre-a-/inter-a-trypsin inhibitors might be similar to that between metalloproteinases induced by macrophages and tissue inhibitors of metalloproteinases by endothelium, which possibly implies that metabolites of pre-a-/inter-a-trypsin inhibitors (UTI) may be dominant in patients with neutrophil-mediated inflammation.…”