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The mode of action of immunosuppressive agents
281 JIM 04097
Bach, J.-F. and T.B. Strom, The Mode of Action of Immunosuppressive Agents, 2nd revised edition (Research Monographs in Immunology, Vol. 9), xx + 420 pp. Elsevier, Amsterdam, 1985. Dfl. 300.00/$111.00, ISBN 0-444-80646-6 The first edition of this monograph was published in 1975 and reviewed in this journal (Vol. 10, 1976, pp. 393-394). Since then the potent and selectively acting drug cyclosporine has been added to the repertoire of available immunosuppressants. Further, the introduction of monoclonal anti-T cell antibodies created a new potential agent for prolonging transplant survival, while the successful application of total lymphoid irradiation (TLI) in the treatment of Hodgkin's disease opened a way for safer administration of ionizing radiation for immunosuppression in special cases of kidney transplantation and in patients with refractory rheumatoid arthritis. These significant innovations have been taken into account in preparing the second, revised and enlarged edition of the book. A new chapter on cyclosporine describes the chemical properties of this cyclic undecapeptide, its pharmacokinetics and toxicity in man, the mechanism of action from T cell binding to IL-2 release inhibition, and the clinical experience accumulated thus far. The authors conclude that cyclosporine, despite undesirable side-effects such as hypertension and long-term nephrotoxicity, has proved efficacious in renal allograft immunosuppression, with little or without concomitant steroid treatment. The improvement over standard methods is reflected in a shorter hospitalization for initial treatment and less frequent re-admission for rejection episodes or complications, resulting in the reduction of financial costs for the patient
by as much as 30%. In the therapy of autoimmune diseases the experience with this drug is limited, but the results in the treatment of uveitis, biliary cirrhosis, and insulin-dependent diabetes mellitus are assessed as highly promising. In the chapter devoted to anti-lymphocyte sera examples are listed of available mouse monoclonal anti-human T cell antibodies, specific for surface antigens on helper or suppressor/cytotoxic cells. The results of preliminary trials with these antibodies in Rhesus monkey skin allografting and in human renal transplantation are reviewed and evaluated. Host reactions against the injected monoclonals (antigenic modulation and xenogeneic sensitization) are discussed and the ways of circumventing them suggested. Finally, in a new chapter dealing with total lymphoid irradiation the results are summarized of studies on the effects of TLI on allograft survival and autoimmune disease in rodents, bone marrow transplantation in dogs, and hepatic and renal transplants in baboons. After reviewing the clinical experience using fractionated TLI combined with traditional therapy in renal transplant patients at risk of high rejection and TLI alone in severe drug-resistant rheumatoid arthritis, the authors conclude that in view of the hazards involved (potential toxicity and possibility of late malignancy) caution ought to prevail in applying this novel therapeutic method in clinical practice. Enriched by these important additions the book continues to be an outstanding source of up-todate information on immunosuppressants and it deserves the attention of medical researchers and practitioners interested in this subject. F. BOREK
JIM 04114
Alitalo, K., P. Partanen and A. Vaheri (eds.), Synthetic Peptides in Biology and Medicine, x +
256 pp. Elsevier, Amsterdam, 1985. 160.00/$59.25, ISBN 0-a.A.A.-80753-5
Dfl.
Bach, J.-F. and T.B. Strom, The Mode of Action of Immunosuppressive Agents, 2nd revised edition (Research Monographs in Immunology, Vol. 9), xx + 420 pp. Elsevier, Amsterdam, 1985. Dfl. 300.00/$111.00, ISBN 0-444-80646-6 The first edition of this monograph was published in 1975 and reviewed in this journal (Vol. 10, 1976, pp. 393-394). Since then the potent and selectively acting drug cyclosporine has been added to the repertoire of available immunosuppressants. Further, the introduction of monoclonal anti-T cell antibodies created a new potential agent for prolonging transplant survival, while the successful application of total lymphoid irradiation (TLI) in the treatment of Hodgkin's disease opened a way for safer administration of ionizing radiation for immunosuppression in special cases of kidney transplantation and in patients with refractory rheumatoid arthritis. These significant innovations have been taken into account in preparing the second, revised and enlarged edition of the book. A new chapter on cyclosporine describes the chemical properties of this cyclic undecapeptide, its pharmacokinetics and toxicity in man, the mechanism of action from T cell binding to IL-2 release inhibition, and the clinical experience accumulated thus far. The authors conclude that cyclosporine, despite undesirable side-effects such as hypertension and long-term nephrotoxicity, has proved efficacious in renal allograft immunosuppression, with little or without concomitant steroid treatment. The improvement over standard methods is reflected in a shorter hospitalization for initial treatment and less frequent re-admission for rejection episodes or complications, resulting in the reduction of financial costs for the patient
by as much as 30%. In the therapy of autoimmune diseases the experience with this drug is limited, but the results in the treatment of uveitis, biliary cirrhosis, and insulin-dependent diabetes mellitus are assessed as highly promising. In the chapter devoted to anti-lymphocyte sera examples are listed of available mouse monoclonal anti-human T cell antibodies, specific for surface antigens on helper or suppressor/cytotoxic cells. The results of preliminary trials with these antibodies in Rhesus monkey skin allografting and in human renal transplantation are reviewed and evaluated. Host reactions against the injected monoclonals (antigenic modulation and xenogeneic sensitization) are discussed and the ways of circumventing them suggested. Finally, in a new chapter dealing with total lymphoid irradiation the results are summarized of studies on the effects of TLI on allograft survival and autoimmune disease in rodents, bone marrow transplantation in dogs, and hepatic and renal transplants in baboons. After reviewing the clinical experience using fractionated TLI combined with traditional therapy in renal transplant patients at risk of high rejection and TLI alone in severe drug-resistant rheumatoid arthritis, the authors conclude that in view of the hazards involved (potential toxicity and possibility of late malignancy) caution ought to prevail in applying this novel therapeutic method in clinical practice. Enriched by these important additions the book continues to be an outstanding source of up-todate information on immunosuppressants and it deserves the attention of medical researchers and practitioners interested in this subject. F. BOREK
JIM 04114
Alitalo, K., P. Partanen and A. Vaheri (eds.), Synthetic Peptides in Biology and Medicine, x +
256 pp. Elsevier, Amsterdam, 1985. 160.00/$59.25, ISBN 0-a.A.A.-80753-5
Dfl.