Therapy with proteolytic enzymes prolongs survival of mouse heart allografts
Gaciong Z.1, Lasek W.1, Jakobisiak M.1,
Stoklosa T.1, Paczek L.1, Heidland A.2.
Therapy with proteolytic enzymes prolongs survival of mouse heart
allografts. Inter. Journal of Tissue Reactions
1997, Vol. XIX, No.1/2, pp. 90 - 91, Abst. 110 - ISSN
0250-0868 149K/245 (19-04-2).
1 Warsaw School of Medicine, Warsaw, Poland. 2 University of
Wuerzburg, Germany.
7th Interscience World Conference on Inflammation, Antirheumatics,
Analgesics, Immunomodulators, Geneva, Switzerland, 19-21 May 97
Abstract: Recently, it has been shown that protease therapy
ameliorates certain immune-mediated diseases. We have shown in rats
with aortic allografts that administration of Phlogenzym®
(trypsin, bromelin, rutosid: PE) alleviates rejection induced
arterial remodelling. In this experimental model proteases inhibited
neointima formation by 59.0% when cross sectional areas were
compared and decreased medial injury as estimated by the integrity
of elastic fibers and smooth muscle cell density. Theoretically,
this effect may be related to the immunomodulating properties of
proteases and/or their ability to affect the response of the
elements of vascular wall. Previously, it has been shown that
proteases selectively remove certain molecules from lymphocytes.
Also, complexes of proteases with physiologic inhibitors
(a2-macroglobulin) have the ability to inactivate growth factors and
cytokines. To investigate if therapy with proteases exerts
immunosuppressive effect in vivo we administered PE to mice with
heart allografts. Fragments of heart tissue from Balb/c (H-2d)
neonates were grafted under the skin of the ear lobe of CBA/H (H-2k)
recipients. Animals were given i.p. injections of PE starting from
day 1 after the surgery and 4 groups were studied each receiving
different daily doses of the enzymes (0.125, 0.5, 1.0, and 2.0 mg).
The function of the grafts was assessed by EKG testing. Control
animals were treated with saline or Cyclosporin A (CsA; 150 mg/kg).
PE given in a dose of 1.0 mg/daily significantly prolonged graft
survival time as compared with the control group
(19.7 ± 7 vs. 13.3 ± 3.8 days, respectively, p < 0.05). Lower doses
of the drug prolonged graft survival, however without reaching
statistically significant difference. There was no notable synergism
in immunosuppressive activity between CsA and PE.
Our results suggest that proteolytic enzymes show direct down
regulation effect on the immune system and its mechanism may be
similar to CsA activity.