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Therapeutic Interventions in the Complement System.
  1. J North

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    Lambris JD, Holers VM, eds. (£90.00.) Humana Press, 2000. ISBN 0 896 03587 5

    The title misled me at first. At last, how to treat my complement deficient patients with more than antibiotics and vaccination. Nope, the back cover hyperbole quickly dashed that thought. What is presented here is a topical review of ways to inhibit complement and its inflammatory role in many diseases.

    The essential role of complement activation is being defined in an increasing number of human diseases. This book details the complement system itself and the search for synthetic or natural inhibitors of the inflammatory pathways of complement. The first chapter gives a concise overview of the complement system and the role of physiological inhibitors. It also summarises several diseases in which turning off complement could be beneficial—for example, ischaemia/reperfusion injury, autoimmune renal disease, and transplantation. It is also the only place in the book where the possible side effects of such treatment are mentioned in any detail. Because the bulk of in vivo research has been performed in animal models, the effects on immunity to infection and immune complex mediated disease in humans needs very careful consideration in planning clinical trials, but this subject receives little attention.

    Subsequent chapters are consistently structured, highly detailed accounts of different areas of the complement system. The chapters do not divide up into the usual “alternative”, “classical”, and “lectin” pathways (although the the membrane attack pathway is dealt with in it's entirety), mimicking the layout in text books, but rather group components with similar physiological roles. Each chapter goes on to explain the rationale behind developing inhibitors relevant to it's own part of the pathway or group of components, how candidate agents are being developed, the use of the agents in animal models, and summaries of any clinical trials up to 1999. The only chapter that meanders a bit is that covering CR3 and CR4 because little tit bits of therapeutics are mixed in with the structure/function background.

    The CR3/CR4 chapter is, however, deserving of a positive comment, because it is the only one that covers enhancing the antitumour role of complement. Considering that tumour expressed complement receptors play a major role in tumour escape from host defences, more could have been included. This subject, on the other hand, goes against the thrust of the rest of the book; so why do we get an excellent section on only one aspect of this field of work?

    Although the basic activation pathways are described in each chapter, the emphasis varies and there is surprisingly little repetition of fine detail between chapters, showing that the editors have done their job well. Cross referencing within the book is limited and pertinent. The chapters that contain a few lines of summary or conclusions at the end get an extra gold star. I find this very useful in books of this calibre because some areas contain more detail than is needed by an individual reader (yes, I skipped bits!), and the summary lets you know if anything crucial has been overlooked.

    The back cover seems to emphasise the coverage of “the new ELISA assays” for assaying complement products. The chapter entitled “Evaluation of complement inhibitors” details (you get a full methodology) the use of haemolytic assays for investigating the effect of putative inhibitors on individual components. It also covers the pros and cons of ELISAs, but anyone looking for details of ELISA methods will be disappointed.

    In summary, there is excellent coverage of the structure and function of complement, broken down into slightly novel but rational areas. Details of how and why new therapeutic agents are being developed is comprehensive, as is the use of animal model studies. Clinical information is necessarily scant, and speculation about future developments fills up the gaps left by the book's title. I see no point in trying to decide specifically whom this book is aimed at because the contents will benefit basic scientists and a wide range of clinicians alike.

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