PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of arthresbiomed central web sitesearch.manuscript submission.see also journal with issn 1478-6354registration.reference to the article.journal front page.
 
Arthritis Res. 2001; 3(Suppl A): P090.
Published online Jan 26, 2001. doi:  10.1186/ar259
PMCID: PMC3273226
Altered migratory capacity of polymorphonuclear leucocytes as an effect of TNF-alpha blockade in patients with rheumatoid arthritis
H Mitterhammer,1 J Hermann,1 G Tilz,1 R Brezinschek,1 U Demel,1 B Yazdani-Biuki,1 T Müller,1 J Gretler,1 S Eder,1 and HP Brezinschek1
1Department of Internal Medicine, Auenbruggerplatz 15, A-8036 Graz, Styria, Austria
Supplement
21st European Workshop for Rheumatology Research
Conference
21st European Workshop for Rheumatology Research
1-4 March 2001
Vienna, Austria
Received January 15, 2001
 
Rheumatoid Arthritis (RA) is associated with progressive joint destruction, functional disability and decreased life expectancy. Althought the underlying cause of RA is unknown, TNF-alpha, a proinflammatory cytokine, contributes to the pathogenesis of synovitis and joint destruction. Anti-TNF-biological response modifiers, such as Etanercept a recombinant human TNF receptor fusion protein, suggest that TNF-alpha-inhibition is a viable approach to control disease activity in RA.
Considering the pivotal role TNF alpha plays in the first line defense against bacterial and fungal infections by polymorphonuclear leucocytes (PMN) it seems important to focus on the PMN function in RA patients, treated with Etanercept. Since a 29% increase in infections of the upper respiratory tract under TNF-alpha blockade has been reported, we investigated inflammatory parameters related to PMN-activity in 6 RA-patients, before and after 3-months of Etanercept treatment without altering their methotrexate and/or glucocorti-coid-medication. The migration of the neutrophils was measured with a standardized whole blood membrane filter assay with and without stimulation by the chemoattractant fMLP. The percentage of migrating PMN (total migration index,TMI) and the relative penetration depth into the filters (distribution characteristics, DC) served to characterize the migratory behaviour of neutrophils. To estimate in vivo granulocyte activation, neutrophil elastase was measured in plasma from RA patients. In addition, PMN-blood count and C-reactive protein as a marker of disease activity, were analysed. TNF-alpha blockade significantly (p < 0,03) reduced the spontaneous and fMLP stimulated median TMI (15.2 vs. 10.9 and 16.5 vs. 11,4, respectively). Moreover the spontaneous and the fMLP-stimulated median DC was reduced under Etanercept-treatment (21.1 vs. 5.9, P < 0.03 and 20.5 vs. 6.6, P < 0.06 respectively). Interestingly, these values were still within the normal range of migratory activity. Furthermore, TNF blockade significantly reduced the median plasma elastase levels (252 vs. 108, p <0,04), as well as the median C reactive protein levels (21 vs. 7 P < 0,035) and the median number of polymorphonuclear leucocytes (7.73 vs. 4.58, P < 0.0001). Of note, plama elastase levels as a sign of systemic PMN-activation were still above the normal range. During the observed treatment period all patients showed an improvement in the inflammatory symptoms of RA (2 had a 70% ACR-response, 3 a 50% and 1 a 20% ACR response). No patients had signs of bacterial or fungal infections. In conclusions, TNF alpha blockade did not suppress PMN migratory activities to levels that are assosciated with higher incidences of infections.
Articles from Arthritis Research are provided here courtesy of
BioMed Central