The effects of cyclosporin A on leucocyte infiltration and procoagulant activity in the mouse delayed hypersensitivity response in vivo.

A model of delayed type hypersensitivity (DTH) to methylated bovine serum albumin was established and characterised in the mouse pleural cavity. Fluid exudate formation was delayed, peaking around 24 h and diminishing by 48-72 h. Exudate leucocyte accumulation was also delayed, rising by 24 h and reaching maximal levels between 24-72 h. Significant PMN leucocyte infiltration was observed early on, although macrophages dominated the reaction from 24 h onwards. Small numbers of lymphoid cells were also observed. Treatment with cyclosporin A (CsA) at 100 mg/kg p.o. around the time of antigen challenge significantly reduced fluid exudate volume but consistently failed to reduce either leucocyte infiltration or the PMN: mononuclear cell ratio throughout the reaction. CsA treatment enhanced DTH exudate leucocyte procoagulant activity (PCA) although leucocyte morphology remained unaltered. The development of carrageenan edema in the hind paws of mice was unaffected by CsA treatment (50-200 mg/kg p.o.). These results suggest that (1) CsA selectively suppresses DTH vascular permeability responses without affecting leucocyte accumulation and (2) CsA does not affect the lymphokine-mediated induction of leucocyte PCA associated with DTH reactions in vivo.