Increased expression of chemokines in patients with Wegener's granulomatosis - modulating effects of methylprednisolone in vitro.
Chemokines, a group of cytokines that attracts and activates leucocyte subpopulations in inflamed tissue, have been associated with the pathogenesis of a number of inflammatory diseases, and some recent reports have suggested their involvement in Wegener's granulomatosis (WG). To elucidate further the possible role of chemokines in WG we examined serum levels of several CC- and CXC-chemokines in WG patients and assessed the ability of corticosteroids to modulate the expression of these mediators in vitro. Our main findings were: (i) WG patients (n = 14) had elevated serum levels of several inflammatory chemokines [i.e. regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8] compared to healthy controls (n = 9), as assessed by enzyme immunoassays (EIAs); (ii) by using EIAs and real-time reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated the ability of methylprednisolone (MP) to down-regulate both the spontaneous and the staphylococcal enterotoxin B (SEB)-induced release of chemokines from peripheral blood mononuclear cells (PBMC) in vitro in both WG patients and controls, possibly involving both transcriptional and post-transcriptional mechanisms; and (iii) the ability of MP to attenuate chemokine secretion was less pronounced in WG patients than in controls, particularly with regard to inhibition of spontaneous release. Our findings suggest a role for chemokines in the pathogenesis of WG. The diminished MP-mediated suppression of chemokines in PBMC from WG patients suggests that more specific modulators of chemokine levels should be investigated in this disorder.
Torheim
E A
EA
Research Institute for Internal Medicine, Medical Department Rikshospitalet, University of Oslo, N-0027 Oslo, Norway.
Yndestad
A
A
Bjerkeli
V
V
Halvorsen
B
B
Aukrust
P
P
Frøland
S S
SS
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood* / Q000235:genetics; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013211:Staphylococcus aureus / Q000276:immunology
D018925:Chemokines; D004768:Enterotoxins; D005938:Glucocorticoids; C031818:enterotoxin B, staphylococcal; D008775:Methylprednisolone