This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Brink, I Articles by Hiepe, F Search for Related Content PubMed PubMed Citation Articles by Brink, I Articles by Hiepe, F Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Lupus Social Bookmarking                         What's this?

Effects of anti-CD4 antibodies on the release of IL-6 and TNF- in whole blood samples from patients with systemic lupus erythematosus

B Thiele

G-R Burmester

G Trebeljahr

Department of Internal Medicine (Rheumatology and Clinical Immunology), Medical School Charité, Humboldt-University, Berlin, Germany

F Emmrich

Department of Clinical Immunology, University of Leipzig, Germany

F Hiepe

Department of Internal Medicine (Rheumatology and Clinical Immunology), Medical School Charité, Humboldt-University, Berlin, Germany

Anti-CD4 antibodies have been recently introduced into the therapy of various autoimmune diseases, among them systemic lupus erythematosus (SLE). Their modes of action are not yet fully understood. Interference with cytokine release may be one possible mechanism. Therefore, the effects of anti-CD4 antibodies on the cytokine release of IL-6 (interleukin-6) and TNF-a (tumor necrosis factor alpha) were investigated in a whole blood culture system. Basal and phytohemagglutin/lipopolysaccharide (PHA/LPS)-stimulated cytokine patterns were compared to cytokine release after the addition of anti-CD4 antibodies (MAX. 166H5) or methylprednisolone in short time whole blood cell culture systems from 12 patients with active SLE, 23 patients with inactive SLE and 12 healthy volunteers. TNF-oc and IL-6 concentrations were determined in the supernatants by ELISA. High disease activity correlated with an increased production of proinflammatory cytokines. Cell cultures of patients with inactive SLE showed a diminished capacity to respond to mitogenic stimulation. Anti-CD4 antibodies added in vitro suppressed significantly the unstimulated production of IL-6 (P < 0.02) in the cell cultures of patients with active SLE and in the PHA/LPS-stimulated cell cultures from both groups of SLE patients (both P < 0.001) and healthy volunteers (P < 0.01). However, MAX.16H5 did not affect the release of TNF-a. In control samples methylprednisolone considerably reduced stimulated and unstimulated IL-6 and TNF-ca production in all SLE patients, irrespective of the disease state, and in all healthy controls.

These data indicate that the proinflammatory cytokines are involved in the pathogenesis of SLE. It is assumed that anti-CD4 antibodies, which can be effective in the treatment of highly active lupus patients, may act via their influence on cytokine release. The decrease of the proinflammatory cytokines IL-6 under therapy with MAX. 16H5 could explain the observations of clinical trials and animal studies which showed a reduction of inflammatory parameters and diminished production of autoantibodies following treatment with anti-CD4 antibodies.

Key Words: systemic lupus erythematosus • anti-CD4 antibody MAX.16H5 • interleukin-6 • tumor necrosis factor-alpha

Lupus, Vol. 8, No. 9, 723-730 (1999)
DOI: 10.1191/096120399678840882


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				K Nissler, D Pohlers, M Huckel, J Simon, R Brauer, and R W Kinne Anti-CD4 monoclonal antibody treatment in acute and early chronic antigen induced arthritis: influence on macrophage activation Ann Rheum Dis, November 1, 2004; 63(11): 1470 - 1477. [Abstract] [Full Text] [PDF]

				A S Wierzbicki Lipid-lowering drugs in lupus: an unexplored therapeutic intervention Lupus, March 1, 2001; 10(3): 233 - 236. [Abstract] [PDF]