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The use of unburned skin from burned animals as homografts with the adjunctive use of convalescent burn serum
The Use of Unburned Skin from Burned Animals as Homografts with the Adjunctive Use of Convalescent Burn Serum MARVIN S. AIlONS, M.I}., B.M.B., S. R. LEg'IS, M.D., J. B. LYNCIt, M.D., ANB T. G. BLOCKEII, J R., M.I)., University o / T e x a s Medical Branch, G a l v e s t o n
Medawar 2° has smnmm'ized tile evidence which identifies rejection of homografts with all immunoh3gic reaction. Although there is much evidence that transplantation immunity is transferable by cells rather than by immune serum,S, lo,~'7 there also has been evidence for the participation of circulating or serum antibodies in h o m o g r a f t rejection, s ' ~ l ' l a ' 2 s Woodruff 26 stated that there was no doubt that homotransplants could stimulate tile formation of humoral antibodies which might be difficult to detect. The evidence summarized by Gorer 13 makes it necessary to abandon a "unitarian" concept of homograft reaction, i.e., the theory that all homografts of all tissues are destroyed by essentially similar mechanisms. As concluded in the book edited by Billingham and Silvers,4 "A more complete understanding of the mechanism of tile processes involved in the rejection of homografts is urgently needed. Attempts to determine the reasons for such variation, and for the a p p a r e n t l y dissimilar effectiveness of the various components of immunity (humoral, cellular, specific and nonspecific) in different circumstances represent one of the most active areas of transplantation research . " The many methods and techniques for prolongation of homograft survival have been summarized by Dunphy and co-workers, iv Whether or not extensive burns in themselves are associated with prolonged survival of homograft is debatable. Case reports have continued From the Department of Surgery, Division of Plastic and Maxillofaciat Surgery, University of Texas Medical Branch, Galveston, Texas. Submitted for publication July 29, 1963. JSR - Vol. IV, No. 6 - June, 1964
to appear in tile literature, s.ls,ls,19,23 ltowever, Bailey et al. t f o u n d no experimental evidence to support the belief that skin homografts survive longer if applied following a severe burn. No studies have been published utilizing unburned skin from burned animals as homografts nor have any reports appeared concerning the use of convalescent burn serum to alter the homograft reaction. Great interest in immune burn serum was generated at fl~e First International Congress on Research in Bums. Blocker and Blocker v have reviewed extensively the Russian and Czech experiments d e s c r i b i n g circulating antigen-antibody levels after burning and have concluded that, although a number of antigenic substances are associated with burned skin and anti gen-anti body ph enomena may oc cur foil owing thermal trauma, their s i g n i f i c a n c e is not entirely clear. ltaving briefly reviewed both the controversial role of serum antibodies on the homograft reaction and the production of immune burn serum, this study was undertaken to help determine if any relationship exists between the immunologic reaction of homograft rejection and the immunologic changes following thermal bums. This was attempted by utilizing unburned skin from burned animals as homografts with tile concurrent use of matched convalescent burn serum. More specifically it was hoped to determine if immune burn serum could "induce tolerance" to skin homografts in burned animals. METItOBS AND MATERIALS Wisconsin Holtzman rats, about 6 months old and weighing an average of 180 grams, were 253
JSR
254 A R O N S . LEWIS, L Y N C t t and B L O C K E R
Fig. I.
d i v i d e d r a n d o m l y into 15 g r o u p s o f 10 a n i m a l s each. These rats served as the donor animals. W i s t a r r a t s , o f s i m i l a r a g e and w e i g h t , a l s o were divided into exactly corresponding groups and w e r e e m p l o y e d a s tile r e c i p i e n t a n i m a l s . All g r o u p s w e r e h o u s e d a s s e p a r a t e c o l o n i e s and m a i n t a i n e d on w a t e r and P u r i n a L a b o r a t o r y C h o w ad l i b i t u m . All r a t s b u r n e d w e r e s u b j e c t e d to a 20 p e r c e n t w e i g h t s c a l d on the d o r s a l surf a c e in w a t e r at 9 0 ° C . for 20 s e c o n d s , a c c o r d i n g to tile m e t h o d o f B a i l e y et at. 2 All s k i n u s e d a s h o m o g r a f t s w a s o b t a i n e d full t h i c k n e s s from the v e n t r a l s u r f a c e of donor a n i m a l s , so t h a t all homografts w e r e normal, u n b u r n e d , b e l l y s k i n . H o m o g r a f t i n g f o l l o w e d the p r i n c i p l e s outl i n e d by B i l l i n g h a m . 3 E a c h g r a f t w a s 2 s q u a r e i n c h e s and w a s f i t t e d into a s u r g i c a l l y e x c i s e d a r e a on t h e d o r s u m of all r e c i p i e n t a n i m a l s with c o n t i n u o u s 4-0 b l a c k s i l k and l e f t e x p o s e d ( F i g . 1). When t h e r e c i p i e n t r a t h a d a d o r s a l burn, the e s c h a r w a s e x c i s e d d o w n to c o m p l e t e l y v i a b l e t i s s u e on the third p o s t b u r n d a y ( F i g s . 2 and 3). C o n v a l e s c e n t s e r u m from b u r n e d r a t s was obt a i n e d o n l y a f t e r a two month p o s t b u r n p e r i o d .
Fig. 2.
Fig. 3.
Homograft three days post-graft.
Eschar three days postburn,
-
Vol. IV, No. 6 - June,
1964
Burn e s c h a r excised.
P o o l e d serum m e a n s t h a t the d o n o r a n i m a l s w e r e exsanguinated via the carotid artery into one s t e r i l e b e a k e r and t h e n t h e b l o o d w a s c e n t r i f u g e d and t h e s e r u m s e p a r a t e d a n d c o l l e c t e d . M a t c h e d serum means that blood was collected via intrac a r d i a c p u n c t u r e from l i v i n g donor a n i m a l s w h i c h t h e r e f o r e s u p p l i e d b o t h s e r u m and h o m o g r a f t to a m a t c h e d r e c i p i e n t r a t . Sernm w a s s t o r e d at m i n u s lO°C. when n e c e s s a r y . All i n j e c t i o n s o f s e r u m and s a l i n e w e r e i n t r a p e r i t o n e a l . B e f o r e b u r n i n g a n d all s u r g i c a l p r o c e d u r e s , t h e a n i m a l s w e r e a n e s t h e t i z e d with e t h e r . P u n c h Table
i.
Donor Rat* Group (Wisconsin Holtzman)
Outline
o/Experinzents
Recipient Rat (Wistar)
I
Unburned
Unburned + saline
II
Unburned
Unburned + pooled normal serum
III
Unburned
Unburned + pooled burn serum
IV
Burned
Unburned + saline
V VI VII VIII
Burned Burned Unburned Burned
Unburned + pooled burn serum Burned + saline Burned + saline Burned + pooled burn serum
IX
Unburned
Burned +pooled normal serum
X
Unburned
Burned + matched normal serum
XI
Burned
Burned + matched burn serum
XII
Unburned
Burned + matched normal serum
XIII
Burned
Burned + matched burn serum
XIV
Unburned
Burned + matched burn serum and changes t
XV
Burned
Burned + matched burn serum and changes t
*All skin homografts were unburned. t See text.
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UNBURNED SKIN AS ItOMOGRAFTS
V o l . . I V , No. 6 - June, 1964
biopsies of all homografts were taken with a s p e c i a l punch having a diameter equal to that of a 16 gauge needle. The s p e c i f i c experimental groups are detailed in T a b l e 1. The time and dose s c h e d u l e of s a l i n e or pooled serum employed in Groups ] through IX is shown in Table 2. The pooled serum for Group III was obtained from an extra group of burned donor animals. In Groups X and XI, 0.50 cc. of matched senlm was administered one hour pregrafting, at the time of grafting and one hour postgrafting. The time and dose s c h e d u l e of pooled serum used in Groups XII through XV i s g i v e n in T a b l e 3. Groups XIV and XV varied from the protocol by the following changes: (1) 240 gin. rats, (2) 10% weight immersion scald burn, (3) eschar e x c i s e d 10 days postburn and (4) 50,000 units aqueous penicillin i n j e c t e d intraperitoneally for six days into recipient homografted animals. An additional Group XVIA served as a control for the serum itself. Into 10 normal Wistar rats 2.0 cc. of pooled normal serum from 30 Wisconsin Holtzman animals was i n j e c t e d intraperiton e a l l y for three c o n s e c u t i v e days.
RESULTS In all tile recipient experimental groups, the skin homografts uniformly were r e j e c t e d at the usual time. Brown p a t c h e s in all the grafts were apparent 6 to 9 days postgrafting and by 12 days postgrafting, all homografts were brown and firm despite the various adjunctive therapy previously described. Biopsy of all the homografts m i c r o s c o p i c a l l y confirmed the characteristic pattern of rejection. The overall mortality rate for all groups prior to the day that graft rejection became apparent was 10 per c e n t . In no group were more than 3 rats ever lost before completion of the experiment. No mortality or morbidity was observed in the Group XVIA contro.1 animals receiving large d o s e s of pooled serum. T a b l e 2. Serum I n j e c t i o n s for Groups I through IX
Day 0 (day of graft) 1 2 3 4
Dose 0.25 0.25 0.50 0.50 0.50
cc. ee. cc. cc. cc.
255
T a b l e 3. Serum I n j e c t i o n s /or Groups XII through X V
Day
Dose
3 (pregraft) 2. l
0 (day of graft) 1 (postgraft) 2
0.50 cc. 0.50 cc. 0.50 ec. 0.50 cc. 0.50 ec. 0.50 cc.
D! SCUSSION As previously noted, the h y p o t h e s i s that the reaction against skin homografts is mediated through cells rather than through serum antibodies has good evidence now. Brent and coworkers 9 have stated that i m m u n e serum containing demonstrably high titers of agglutinating antibodies usually weakens thehomograft reaction, that no correlation e x i s t s between the p r e s e n c e or a b s e n c e of hemagglutinins and the p r e s e n c e or absence of transplantation immunity, and that the work of Stetson and Demopoulous as could not be confirmed..The goldfish studies of Hildemann 16 also confirm the now generally a c c e p t e d belief that there is no correlation between the p r e s e n c e or a b s e n c e of specific circulating antibodies and the p r e s e n c e or a b s e n c e of transplantation immunity. In the early work of Rhode as cited by P e e r , 22 the survival of homotransplants a c t u a l l y was shortened by the injection of plasma, serum, skin e x t r a c t s and skin a u t o l y s a t e s . As regards burn immunology, Sell aa and Graber14 have failed to confirm the HeLa cell cytotoxicity t e s t of Rosenthal. Moyer and coworkers z~ were unable to reproduce the work of Feodorov and concluded that their studies dic] notsupport tile concept of a s u b s t a n c e produced by burn injury that is antigenic to unburned animals. Blocker s believes that the b e n e f i t s reportedly derived from the administration of c o n v a l e s c e n t burn serum probably are related to antibodies against burn wound microorganisms rather than to specific antigens produced in burned skin or in other damaged t i s s u e s , including elements of the blood. The r e s u l t s of the animal investigations herein reported, then, lend support to the above mentioned current immunologic theories.
256 ARONS, LE~IS, LYNCIt and BLOCKER
SUMMARY No experimental evidence has been found to support the belief that unburned skin homografts from unburned animals survive longer if applied to other burned aninrals. The adjunctive use of convalescent burn serum in no way altered the rejection of these homografts. There appears to be no clinical relationship between the homograft reaction and postburn immunologi c ch an ges.
REFERENCES 1. Bailey, B.N., Lewis, S.R., and Blocker, T.G., Jr.: Influence of thermal trauma per se on homograft survival-an experimental study. Texas Rep. Biol. & Med., 20:30, 1962. 2. Bailey, B.N., Lewis, S.R., and Blocker, T.G., Jr.: Standardization of experimental burns in the laboratory rat. Texas Rep. Biol. & Med., 20:20, 1962. 3. Billingham, R.E., and Medawar, P.B.: The technique of free skin grafting in mammals. J. Exper. Biol,, 28:385, 1951. 4. Billingham, R.E., and Silvers, W.K.: Transplantation of Tissues and Cells. The Wistar Institute Press, Philadelphia, 1961. 5. Blocker, T.G,, Jr.: Annual Report, U.S. Army Contract ?'A-49-007-MD-447, University of Texas Med~ al Branch, Galveston. I956, p. 176. 6. Blocker, T.G., ~'.: Personal communication. 7. Blocker, T,G,, .~r., and Blocker, V.: New concepts in burn physiology and burn treatment. In Allg~'wer, M., Ed.: Progress in Surgery. Vol. III, S. Karger, Basel and New York, 1963. 8. Bollag, W.S.: Demonstration of antibodies following homograft. Transplant. Bull,i 3:43, 1956. 9. Brent, L., Brown, J.B., and Medawar, P.B.: Skin transplantation immunity in relation t0hypersensitivity reactions of the delayed type. In Biological Problems of Grafting-a Symposium. Charles C Thomas, Springfield, Ill., 1959, pp: 64-82. 10. Burner, F.M., and Fenner, F.J.: The Production of Antibodies. The Macmillan Co., New York, 1949.
JSR - Vol. IV, No. 6 - ]u,~e, 1964
11. Good, R.A., Varco, R.L., Aust, J.R., and Zak, S.J.: Transplantation studies in patients with agammaglobulinemia. Ann. New York Acad. Sc., 64:882, 1957. 12. Gorer, P.A.: The antibody response to skin homografts in mice. Ann. New York Acad. Sc., 59:356, 1955. 13. Gor.er, P.A.: Somerecent work on tumor immunity. Advances Cancer Res., 4:149, 1956. 14. Graber, C.D.: hnmunotransfusion in the treatment of burns. Proceedings of Subcommittee on P l a s m a , National Academy of SciencesNational Research Council, 1961. 15. ttelsinger, N.J., and ltelsinger, P.: Brephoplastic transplantation of skin-case report, Transplant. Bull., 4:24, 1957. 16. Hildemann, W.t[.: Tissue transplantation immunity in goldfish. Immunology, 1:46, 1958. 17. Jacob, S.W., Gowing, D., and Dunphy, J.E.: Transplantation of tissues. Am. J. Surg., 98:55, 1959. 18. Kay, G.D.: Prolonged survival of a skin homograft in a patient with very extensive burns. Ann. New York Acad. Sc., 64:767, 1957. 19. Konuralp, H.Z.: Permanent take of homografts in a burned patient-case report. Transactions of the International Society of Plastic Surgeons, Second Congress, London, 1959. E. and S. Livingstone, Edinburgh, 1960, pp. 475-478. 20. Medawar, P.B.: The immunity of transplantation. ttarvey Lect., 52:144, 1956/57. 21. Newton, W.T., Fujii, U., and Moyer, C.A.: Immune specificity of burn toxin. Arch. Surg., 85:62, 1962. 22. Peer, L.A.: Transplantation of Tissues. Vol. 1. Williams and Wilkins Co., Baltimore, 1955. 23. Rogers, B.O.: The genetics of skin homotransplantation in the human. Ann. New York Acad. Sc., 64:741, 1957. 24. Sell, K.: Investigations concerning a proposed toxin and antitoxin in the serum of burned patients. Proceedings of Subcommittee on Plasma, National Academy of Sciences-National Research Council, 1961. 25. Stetson, C.A., and Demopoulos, R.: Reactions of skin homografts with specific immune sera. Nnn. New York Acad. So., Third Transplantation Conference, 73:687, 1958. 26. Woodruff, M.F.: The Transplantation of Tissues and Organs. Charles C Thomas, Springfield, II1., 1960.
Medawar 2° has smnmm'ized tile evidence which identifies rejection of homografts with all immunoh3gic reaction. Although there is much evidence that transplantation immunity is transferable by cells rather than by immune serum,S, lo,~'7 there also has been evidence for the participation of circulating or serum antibodies in h o m o g r a f t rejection, s ' ~ l ' l a ' 2 s Woodruff 26 stated that there was no doubt that homotransplants could stimulate tile formation of humoral antibodies which might be difficult to detect. The evidence summarized by Gorer 13 makes it necessary to abandon a "unitarian" concept of homograft reaction, i.e., the theory that all homografts of all tissues are destroyed by essentially similar mechanisms. As concluded in the book edited by Billingham and Silvers,4 "A more complete understanding of the mechanism of tile processes involved in the rejection of homografts is urgently needed. Attempts to determine the reasons for such variation, and for the a p p a r e n t l y dissimilar effectiveness of the various components of immunity (humoral, cellular, specific and nonspecific) in different circumstances represent one of the most active areas of transplantation research . " The many methods and techniques for prolongation of homograft survival have been summarized by Dunphy and co-workers, iv Whether or not extensive burns in themselves are associated with prolonged survival of homograft is debatable. Case reports have continued From the Department of Surgery, Division of Plastic and Maxillofaciat Surgery, University of Texas Medical Branch, Galveston, Texas. Submitted for publication July 29, 1963. JSR - Vol. IV, No. 6 - June, 1964
to appear in tile literature, s.ls,ls,19,23 ltowever, Bailey et al. t f o u n d no experimental evidence to support the belief that skin homografts survive longer if applied following a severe burn. No studies have been published utilizing unburned skin from burned animals as homografts nor have any reports appeared concerning the use of convalescent burn serum to alter the homograft reaction. Great interest in immune burn serum was generated at fl~e First International Congress on Research in Bums. Blocker and Blocker v have reviewed extensively the Russian and Czech experiments d e s c r i b i n g circulating antigen-antibody levels after burning and have concluded that, although a number of antigenic substances are associated with burned skin and anti gen-anti body ph enomena may oc cur foil owing thermal trauma, their s i g n i f i c a n c e is not entirely clear. ltaving briefly reviewed both the controversial role of serum antibodies on the homograft reaction and the production of immune burn serum, this study was undertaken to help determine if any relationship exists between the immunologic reaction of homograft rejection and the immunologic changes following thermal bums. This was attempted by utilizing unburned skin from burned animals as homografts with tile concurrent use of matched convalescent burn serum. More specifically it was hoped to determine if immune burn serum could "induce tolerance" to skin homografts in burned animals. METItOBS AND MATERIALS Wisconsin Holtzman rats, about 6 months old and weighing an average of 180 grams, were 253
JSR
254 A R O N S . LEWIS, L Y N C t t and B L O C K E R
Fig. I.
d i v i d e d r a n d o m l y into 15 g r o u p s o f 10 a n i m a l s each. These rats served as the donor animals. W i s t a r r a t s , o f s i m i l a r a g e and w e i g h t , a l s o were divided into exactly corresponding groups and w e r e e m p l o y e d a s tile r e c i p i e n t a n i m a l s . All g r o u p s w e r e h o u s e d a s s e p a r a t e c o l o n i e s and m a i n t a i n e d on w a t e r and P u r i n a L a b o r a t o r y C h o w ad l i b i t u m . All r a t s b u r n e d w e r e s u b j e c t e d to a 20 p e r c e n t w e i g h t s c a l d on the d o r s a l surf a c e in w a t e r at 9 0 ° C . for 20 s e c o n d s , a c c o r d i n g to tile m e t h o d o f B a i l e y et at. 2 All s k i n u s e d a s h o m o g r a f t s w a s o b t a i n e d full t h i c k n e s s from the v e n t r a l s u r f a c e of donor a n i m a l s , so t h a t all homografts w e r e normal, u n b u r n e d , b e l l y s k i n . H o m o g r a f t i n g f o l l o w e d the p r i n c i p l e s outl i n e d by B i l l i n g h a m . 3 E a c h g r a f t w a s 2 s q u a r e i n c h e s and w a s f i t t e d into a s u r g i c a l l y e x c i s e d a r e a on t h e d o r s u m of all r e c i p i e n t a n i m a l s with c o n t i n u o u s 4-0 b l a c k s i l k and l e f t e x p o s e d ( F i g . 1). When t h e r e c i p i e n t r a t h a d a d o r s a l burn, the e s c h a r w a s e x c i s e d d o w n to c o m p l e t e l y v i a b l e t i s s u e on the third p o s t b u r n d a y ( F i g s . 2 and 3). C o n v a l e s c e n t s e r u m from b u r n e d r a t s was obt a i n e d o n l y a f t e r a two month p o s t b u r n p e r i o d .
Fig. 2.
Fig. 3.
Homograft three days post-graft.
Eschar three days postburn,
-
Vol. IV, No. 6 - June,
1964
Burn e s c h a r excised.
P o o l e d serum m e a n s t h a t the d o n o r a n i m a l s w e r e exsanguinated via the carotid artery into one s t e r i l e b e a k e r and t h e n t h e b l o o d w a s c e n t r i f u g e d and t h e s e r u m s e p a r a t e d a n d c o l l e c t e d . M a t c h e d serum means that blood was collected via intrac a r d i a c p u n c t u r e from l i v i n g donor a n i m a l s w h i c h t h e r e f o r e s u p p l i e d b o t h s e r u m and h o m o g r a f t to a m a t c h e d r e c i p i e n t r a t . Sernm w a s s t o r e d at m i n u s lO°C. when n e c e s s a r y . All i n j e c t i o n s o f s e r u m and s a l i n e w e r e i n t r a p e r i t o n e a l . B e f o r e b u r n i n g a n d all s u r g i c a l p r o c e d u r e s , t h e a n i m a l s w e r e a n e s t h e t i z e d with e t h e r . P u n c h Table
i.
Donor Rat* Group (Wisconsin Holtzman)
Outline
o/Experinzents
Recipient Rat (Wistar)
I
Unburned
Unburned + saline
II
Unburned
Unburned + pooled normal serum
III
Unburned
Unburned + pooled burn serum
IV
Burned
Unburned + saline
V VI VII VIII
Burned Burned Unburned Burned
Unburned + pooled burn serum Burned + saline Burned + saline Burned + pooled burn serum
IX
Unburned
Burned +pooled normal serum
X
Unburned
Burned + matched normal serum
XI
Burned
Burned + matched burn serum
XII
Unburned
Burned + matched normal serum
XIII
Burned
Burned + matched burn serum
XIV
Unburned
Burned + matched burn serum and changes t
XV
Burned
Burned + matched burn serum and changes t
*All skin homografts were unburned. t See text.
JSR -
UNBURNED SKIN AS ItOMOGRAFTS
V o l . . I V , No. 6 - June, 1964
biopsies of all homografts were taken with a s p e c i a l punch having a diameter equal to that of a 16 gauge needle. The s p e c i f i c experimental groups are detailed in T a b l e 1. The time and dose s c h e d u l e of s a l i n e or pooled serum employed in Groups ] through IX is shown in Table 2. The pooled serum for Group III was obtained from an extra group of burned donor animals. In Groups X and XI, 0.50 cc. of matched senlm was administered one hour pregrafting, at the time of grafting and one hour postgrafting. The time and dose s c h e d u l e of pooled serum used in Groups XII through XV i s g i v e n in T a b l e 3. Groups XIV and XV varied from the protocol by the following changes: (1) 240 gin. rats, (2) 10% weight immersion scald burn, (3) eschar e x c i s e d 10 days postburn and (4) 50,000 units aqueous penicillin i n j e c t e d intraperitoneally for six days into recipient homografted animals. An additional Group XVIA served as a control for the serum itself. Into 10 normal Wistar rats 2.0 cc. of pooled normal serum from 30 Wisconsin Holtzman animals was i n j e c t e d intraperiton e a l l y for three c o n s e c u t i v e days.
RESULTS In all tile recipient experimental groups, the skin homografts uniformly were r e j e c t e d at the usual time. Brown p a t c h e s in all the grafts were apparent 6 to 9 days postgrafting and by 12 days postgrafting, all homografts were brown and firm despite the various adjunctive therapy previously described. Biopsy of all the homografts m i c r o s c o p i c a l l y confirmed the characteristic pattern of rejection. The overall mortality rate for all groups prior to the day that graft rejection became apparent was 10 per c e n t . In no group were more than 3 rats ever lost before completion of the experiment. No mortality or morbidity was observed in the Group XVIA contro.1 animals receiving large d o s e s of pooled serum. T a b l e 2. Serum I n j e c t i o n s for Groups I through IX
Day 0 (day of graft) 1 2 3 4
Dose 0.25 0.25 0.50 0.50 0.50
cc. ee. cc. cc. cc.
255
T a b l e 3. Serum I n j e c t i o n s /or Groups XII through X V
Day
Dose
3 (pregraft) 2. l
0 (day of graft) 1 (postgraft) 2
0.50 cc. 0.50 cc. 0.50 ec. 0.50 cc. 0.50 ec. 0.50 cc.
D! SCUSSION As previously noted, the h y p o t h e s i s that the reaction against skin homografts is mediated through cells rather than through serum antibodies has good evidence now. Brent and coworkers 9 have stated that i m m u n e serum containing demonstrably high titers of agglutinating antibodies usually weakens thehomograft reaction, that no correlation e x i s t s between the p r e s e n c e or a b s e n c e of hemagglutinins and the p r e s e n c e or absence of transplantation immunity, and that the work of Stetson and Demopoulous as could not be confirmed..The goldfish studies of Hildemann 16 also confirm the now generally a c c e p t e d belief that there is no correlation between the p r e s e n c e or a b s e n c e of specific circulating antibodies and the p r e s e n c e or a b s e n c e of transplantation immunity. In the early work of Rhode as cited by P e e r , 22 the survival of homotransplants a c t u a l l y was shortened by the injection of plasma, serum, skin e x t r a c t s and skin a u t o l y s a t e s . As regards burn immunology, Sell aa and Graber14 have failed to confirm the HeLa cell cytotoxicity t e s t of Rosenthal. Moyer and coworkers z~ were unable to reproduce the work of Feodorov and concluded that their studies dic] notsupport tile concept of a s u b s t a n c e produced by burn injury that is antigenic to unburned animals. Blocker s believes that the b e n e f i t s reportedly derived from the administration of c o n v a l e s c e n t burn serum probably are related to antibodies against burn wound microorganisms rather than to specific antigens produced in burned skin or in other damaged t i s s u e s , including elements of the blood. The r e s u l t s of the animal investigations herein reported, then, lend support to the above mentioned current immunologic theories.
256 ARONS, LE~IS, LYNCIt and BLOCKER
SUMMARY No experimental evidence has been found to support the belief that unburned skin homografts from unburned animals survive longer if applied to other burned aninrals. The adjunctive use of convalescent burn serum in no way altered the rejection of these homografts. There appears to be no clinical relationship between the homograft reaction and postburn immunologi c ch an ges.
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JSR - Vol. IV, No. 6 - ]u,~e, 1964
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