title: Effects of infliximab and hydrocortisone on in vitro cytokine responses after stimulation with lipopolysaccharide.
abstract: BACKGROUND
  Both glucocorticosteroids and biologic drugs such as the tumor necrosis factor (TNF)-α antagonist infliximab are used often in the treatment of rheumatoid arthritis or inflammatory bowel disease. In severe disease, or if allergic reactions occur during treatment with infliximab, combined therapy with these drugs often is instituted. Combining infliximab and glucocorticosteroids may increase substantially the risk of severe opportunistic infections or dissemination of malignant tumors because of their additive effects as immunosuppressants.
  
  
  METHODS
  In a whole-blood in vitro model, we studied the influence of different doses of infliximab and hydrocortisone, either separately or in combination, on the synthesis of selected cytokines after stimulation with lipopolysaccharide (LPS).
  
  
  RESULTS
  Hydrocortisone in therapeutic serum concentrations significantly inhibited the expression of a majority of the cytokines tested. Infliximab, in serum concentrations relevant to clinical situations, inhibited TNF-α activity significantly. This effect was potentiated when infliximab was combined with hydrocortisone. Similar effects were found using a low dose of infliximab combined with hydrocortisone. Infliximab alone inhibited the expression of the cytokines interleukin (IL)-1 receptor antagonist, monocyte chemoattractant protein-1, IL-8, and IL-12. Hydrocortisone in combination with low-dose infliximab potentiated the suppressive effects on TNF-α, IL-1β, IL-8, and macrophage inflammatory protein-1α synthesis.
  
  
  CONCLUSIONS
  Immune-modulating effects of infliximab were found both in clinically relevant doses and, most notably, in low doses reflecting serum concentrations found commonly in patients several months after the last injection. Infliximab potentiates the suppressive effects of hydrocortisone on cytokine synthesis.
authors: Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway. tomruud@online.no
authors: Tom Erik
authors: TE
authors: Ruud
authors: Yngvar
authors: Y
authors: Gundersen
authors: Claus Danckert
authors: CD
authors: Krohn
authors: Ola
authors: O
authors: Sveen
authors: Ansgar O
authors: AO
authors: Aasen
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D004357:Drug Synergism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D000069285:Infliximab; D008070:Lipopolysaccharides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D000069285:Infliximab; D006854:Hydrocortisone