Modulation of adhesion and chemotaxis of human neutrophils by cortisol, transforming growth factor-beta and antiinflammatory drugs

Neutrophils are the first cells that accumulate in response to stimuli from the arising inflammation site. We have studied the influence of commonly u sed antiinflammatory (acetylsalicylic acid) and immunosuppressive (cyclospo rin A, methotrexate) drugs and endogenous substances of antiinflammatory ac tivity (cortisol, transforming growth factor-beta; TGF-beta) on the interde pendent phenomena of cell motility and adhesion. Neutrophils from healthy s ubjects were preincubated with various concentrations of these substances a nd adhesion to plastic-bound monoclonal antibodies to CD11la/CD18, CD11c/CD 18 and CD44 was determined. We have found that the studied drugs significan tly lowered adhesion (by 40%) of neutrophils to the ligands. Simultaneously , cell motility was investigated according to the Boyden method. We found a significant dose-dependent increase in the motility of this cells in a ran ge comparable to conventional chemoattractants for neutrophils. These data indicate that simultaneous enhancement of motility and reduction of adhesio n might be a common pathway for the mechanisms of action of the most common antiinflammatory drugs.