Influence of Mycophenolate Mofetil (MMF) on the acute and chronic rejection and on CD 11a/CD 18 expression after allogeneic lung transplantation (LTX) in a rat model

T. Pühler; E. Lesser; M. v d Brelie; C. Hass; M. Frahm; M. Ernst; H. Wottge; J. Cremer; S. Hirt

doi:10.1055/s-2005-861991

The Thoracic and Cardiovascular Surgeon, Table of Contents

Influence of Mycophenolate Mofetil (MMF) on the acute and chronic rejection and on CD 11a/CD 18 expression after allogeneic lung transplantation (LTX) in a rat model

T Pühler ¹, E Lesser ¹, M v.d. Brelie ¹, C Hass ¹, M Frahm ¹, M Ernst ¹, H Wottge ², J Cremer ¹, S Hirt ¹

¹University SH Campus Kiel, Cardiovascular Surgery, Kiel
²University SH Campus Kiel, Immunology, Kiel

Abstract

Objectives: In a rat model (F344>WKY) we could clearly demonstrate, that without immunosuppression (IS) after LTX acute rejection (AR) and CD11a-/CD18-expression reaches the maximum at day 14 followed by a severe chronic rejection (CR) with a decrease in CD11a-/CD18-expression. We investigated the influence of a methylprednisolon (MP)-bolus application before and at the timepoint of AR and furthermore the efficacy of MMF on AR and CR after too late rejection therapy.

Material and Methods: In group-I (n=20) 10mg/kgbw-MP was applicated intraperitoneally (i.p.) at day 9+10+11. In group-II (n=20) 10mg/kgbw-MP i.p. at day 14+15+16. Group-III (n=20) received additional treatment with 30mg/kgbw-MMF i.p. daily from day 14. 5 rats of each group were sacrified at day 20, 30, 60, 100.

Results: In group-I AR is treated effectively with MP and no CR appears. In group-II after MP-therapy AR was treated partly but severe CR appeared at day 60+100. Between groupI+II was no significant difference between CD11a/CD18-expression. In group-III the amount of AR at day 20+30 was less impressive than in group-II. At day 60+100 CR appeared wheras vascular damage in contrast to group-II was less distinct. In group-III CD11a-/CD18-expression was significant lower than in group I+II.

Conclusions: Early MP-treatment minimizes AR. The graft develops no CR (group-I). Late MP-therapy at the zenith of AR (group-II) fails to controlAR and severeCR appears. Additional MMF-application (group-III) reduces vascular and bronchial AR and vascular CR is obvious reduced, but there is no effect on bronchial CR. CD11a/CD18-expression is significant lower in groupIII.