Prevention of cytokine-induced changes in leukocyte adhesion receptors by nonsteroidal antiinflammatory drugs from the oxicam family

Arthritis Rheum. 1997 Jan;40(1):143-53. doi: 10.1002/art.1780400119.


Objective: To explore the effect of the nonsteroidal antiinflammatory drugs (NSAIDs) piroxicam and meloxicam on quantitative and qualitative changes in leukocyte adhesion receptors induced by cytokines and other activation stimuli.

Methods: The expression of CD11b and L-selectin during neutrophil activation with tumor necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), FMLP, phorbol myristate acetate (PMA), and calcium ionophore A23187 was assessed by flow cytometry. Enzyme-linked immunosorbent assays were used to quantitate soluble L-selectin shed after neutrophil stimulation. Enzyme release was measured to determine neutrophil degranulation by proinflammatory stimuli. Changes in affinity state of beta 1 and beta 2 integrins after neutrophil and T lymphocyte stimulation were assessed, by flow cytometry, using the monoclonal antibodies (MAb) HUTS-21 (anti-beta 1) and CBRM1/5 (anti-CD11b), which recognize activation-dependent epitopes on these two integrins.

Results: Pretreatment of neutrophils with either NSAID prevented the changes in L-selectin and CD11b expression induced by TNF alpha, GM-CSF, and FMLP, but not those induced by PMA or A23187. Furthermore, piroxicam significantly decreased the amount of L-selectin shed by cytokine-treated neutrophils, whereas it did not exert this effect on PMA- or A23187-treated neutrophils. Piroxicam also decreased the release of gelatinase and lysozyme induced by TNF alpha, but not by PMA. Interestingly, piroxicam prevented the conformational changes that beta 2 integrins underwent upon activation of neutrophils: the appearance of the activation epitope of CD11b, detected by the CBRM1/5 MAb, was blocked by piroxicam in TNF alpha-treated neutrophils. Moreover, in chemokine-treated T lymphocytes, the expression of activation epitopes on beta 1 integrins was also diminished by piroxicam. In contrast, this NSAID did not affect the beta 1 integrin conformational changes induced by PMA or Mn++.

Conclusion: Our results indicate that members of the oxicam family are able to interfere with events of neutrophil function, such as their degranulation and cytokine-mediated activation changes in adhesion molecules, both in neutrophils and in lymphocytes. Such effects may significantly contribute to the antiinflammatory activity of these drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • CD11 Antigens / drug effects
  • Cells, Cultured
  • Chemokines / antagonists & inhibitors*
  • Cytoplasmic Granules / drug effects
  • Flow Cytometry
  • Humans
  • Integrins / biosynthesis
  • Integrins / drug effects
  • L-Selectin / drug effects
  • Lymphocytes / drug effects*
  • Meloxicam
  • Neutrophils / drug effects*
  • Piroxicam / pharmacology*
  • Thiazines / pharmacology*
  • Thiazoles / pharmacology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • CD11 Antigens
  • Chemokines
  • Integrins
  • Thiazines
  • Thiazoles
  • L-Selectin
  • Piroxicam
  • Meloxicam