In vivo effects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis.
15-Deoxyspergualin (DSG) is an alternative treatment modality for Wegener's granulomatosis (WG) patients refractory to conventional treatment. Nevertheless, it is unclear how DSG modulates disease activity in these patients. This study was conducted to investigate which parameters of adaptive and acquired immunity were influenced during two subsequent cycles of DSG treatment. Emphasis was put upon T cell and monocyte activation, neutrophil function and surface expression of proteinase-3 (PR-3). Anti-CD3/anti-CD28 and interleukin (IL)-15/IL-7-mediated T cell proliferation were assessed by fluorescence activated cell sorter (FACS) analysis using carboxyfluorescein succinimidyl ester (CSFE) labelling. Interferon (IFN)-gamma and IL-10 production were determined in the supernatants of these cultures by enzyme-linked immunosorbent assay. Monocyte activation was assessed in lipopolysaccharide (LPS)-stimulated whole blood, using tumour necrosis factor (TNF)-alpha as read-out. Neutrophil function was determined by measuring oxidative burst, chemotaxis and phagocytosis. T cell activation markers and PR3 expression were measured by FACS. All parameters were determined directly before and after each DSG cycle. Anti-CD3/anti-CD28-mediated T cell proliferation was reduced directly after DSG treatment. Directly before a subsequent cycle of DSG was started, T cell proliferation was increased. Similar findings were observed for IFN-gamma and IL-10 production by T cells. DSG did not influence IL-15/IL-7-mediated T cell proliferation. LPS-mediated TNF-alpha production was also impaired directly after DSG treatment. No influence on T cell activation markers, neutrophil function and surface PR-3 expression was observed in peripheral blood of these patients. Our data demonstrate that DSG influences T cell and monocyte activation in a reversible fashion. Although DSG causes neutropenia in these patients, it does not influence neutrophil function.
Kälsch
A-I
AI
Department of Clinical Chemistry, University Hospital Mannheim, University of Heidelberg, Germany. anna-isabelle.kaelsch@med5.ma.uni-heidelberg.de
Schmitt
W H
WH
Breedijk
A
A
Marinaki
S
S
Weigerding
S
S
Nebe
T C
TC
Nemoto
K
K
van der Woude
F J
FJ
Yard
B A
BA
Birck
R
R
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006146:Guanidines; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; C037258:gusperimus