Modulation of cytokine release from human monocytes by drugs used in the therapy of inflammatory bowel diseases.
BACKGROUND
Cytokines produced in the gut mucosa play an important role in the pathogenesis of inflammatory bowel diseases (IBD). To determine whether drugs used in the treatment of these diseases modulate cytokine synthesis, we investigated their effects on endotoxin-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 release by elutriation-purified human monocytes in vitro.


METHODS
Drugs tested were dexamethasone, 5-aminosalicylic acid, sulphapyridine and zileuton (a 5-lipoxygenase inhibitor). Monocytes were isolated and stimulated with endotoxin, and TNF, IL-1 and IL-6 levels were determined using an enzyme-linked immunosorbent assay.


RESULTS
Monocyte stimulation with endotoxin resulted in an average TNF release of 2464 +/- 64 pg/10(6) cells, IL-1 release of 616 +/- 47 pg/10(6) cells and IL-6 release of 2259 +/- 148 pg/10(6) cells. Addition of dexamethasone resulted in a reduction of TNF, IL-1 and IL-6 release to below background levels. Sulphapyridine significantly reduced TNF and induced IL-1 release in a dose-dependent fashion, but had no significant effect on IL-6 release. 5-Aminosalicylic acid did not modulate IL-6 synthesis, but significantly reduced IL-1 and enhanced TNF synthesis. Zileuton reduced TNF and IL-6 release, but enhanced IL-1 release.


CONCLUSIONS
We conclude that these anti-inflammatory drugs are able to modulate cytokine release by human monocytes. Further studies are needed to determine whether these effects are related to their therapeutic efficacy in IBD.
D000636:Aminosalicylic Acids / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D019804:Mesalamine; D013427:Sulfapyridine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000636:Aminosalicylic Acids; D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019804:Mesalamine; D003907:Dexamethasone; C063449:zileuton; D006918:Hydroxyurea; D013427:Sulfapyridine