Effect of xanthine derivates and dexamethasone on Streptococcus pneumoniae-stimulated production of tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta), and IL-10 by human leukocytes.
The present study concerns the release of the proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha and of the anti-inflammatory cytokine IL-10 by human leukocytes in whole blood during stimulation with Streptococcus pneumoniae and the effects of various xanthine derivates, i.e., pentoxifylline (PTX), caffeine, and theofylline, and of dexamethasone (DXM). All three xanthine derivates and DXM inhibited the release of tumor necrosis factor alpha, PTX being the most effective. PTX, theofylline, and DXM inhibited the release of IL-1 beta, but caffeine did not affect IL-1 beta release. The release of IL-10 was significantly reduced by PTX at 24 h and by caffeine at 48 h, but DXM increased the release of this cytokine. In sum, the results of this study demonstrate that DXM inhibits only the release of proinflammatory cytokines but not of the anti-inflammatory cytokine IL-10 by human leukocytes, while PTX is the most potent inhibitor of both proinflammatory and anti-inflammatory cytokines.
van Furth
A M
AM
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Seijmonsbergen
E M
EM
Langermans
J A
JA
van der Meide
P H
PH
van Furth
R
R
D002110:Caffeine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D010431:Pentoxifylline / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013806:Theophylline / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology*
D016207:Cytokines; D005938:Glucocorticoids; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D014970:Xanthines; D016753:Interleukin-10; D002110:Caffeine; D003907:Dexamethasone; D013806:Theophylline; D010431:Pentoxifylline