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Cytokine networks in the lung
Abstracts 645
Preface to abstracts
All of the free communications have been abstracted by the authors concerned and in addition, three of the invited speakers, Dr F. Balkwill (Imperical Cancer Research Fund) and Drs P. Jeffery and G. Laurent (both of the National Heart and Lung Institute) have kindly provided summaries of their presentations which were: 'An introduction to the cytokines', 'Cytokines and asthma', and 'Cytokines and pulmonary fibrosis' respectively. For completeness, the following paragraphs briefly highlight some of the major points from the presentations of the remaining invited speakers.
Measurement of cytokines in clinical samples STEPHEN POOLE, National Institute for Biological Standards and Control In this presentation, we learnt the relative advantages and disadvantages of bio- and immunoassays for cytokines. We were also reminded that a bioassay and an immunoassay for the same cytokine rarely yield identical results, since, of course, they are measuring different things. For example, the presence of an antagonist to a cytokine receptor in a biological sample, will reduce the bioactivity of that cytokine, but may or may not affect its immunoreactivity, Complex biological samples such as lung lavage and plasma contain many substances which can block antibody binding sites or conversely, to which antibodies may adhere non-specifically. Dr Poole therefore stressed the importance of adopting a meticulous and stringent approach to the development of new irnmunoassays. He emphasized that, to ensure specificity, the assay must give parallel standard curves in biological fluids and in a simple model system.
Cytokine networks in the lung STEVEN KUNKEL, Ann Arbor, Michigan, U.S.A. Our first overseas speaker, Professor Kunkel, expounded on the involvement of cytokine networks in the maintenance of chronic inflammation in several experimental models in the mouse lung. Intravenous injection of Sephadex beads carrying a purified protein derivative from Mycobacterium embolize in the lung provoking a THI lymphocyte-driven response, characterized by the production of IL-2 and I F N 7. In contrast, if the beads are linked to an antigen isolated from eggs of Schistosoma mansoni, the response is Tn2-1ymphocyte driven, characterized by IL-1 synthesis and results in the production of long-lasting pulmonary granulomata. Interestingly, in the latter model, levels of IL-1 receptor antagonist (IRAP) rise as those of IL-1 activity fall. Passive immunization of the animals to remove the IRAP results in an increased growth of the granulomata, indicating that the local synthesis and release of this antagonist is an important check to limit granuloma size. Professor Kunkel discussed the roles of a number of cytokines in experimental and clinical models of chronic pulmonary inflammation. Intravenous dosing with Sephadex beads impregnated with IL-4 or MCP-1 (monocyte chemotactic peptide) induced the development of granulomata, IL-4 acting indirectly by inducing the synthesis of MCP-1 and hence, attracting the mononuclear cells which are prerequisites of granuloma formation. Interestingly, MCP-1 is made by lung fibroblasts from patients with a granulomatous disease, sarcoidosis, and is detectable at high levels in their lung lavage, but is not found in samples from bronchitic or control subjects. This supports the concept that MCP-1 may play a similar role in sarcoidosis to that seen in the animal model. Finally, the speaker stressed that there is considerable redundancy in the cytokine system and thus, inhibition or deletion of a single cytokine is unlikely to block chronic inflammation.
Preface to abstracts
All of the free communications have been abstracted by the authors concerned and in addition, three of the invited speakers, Dr F. Balkwill (Imperical Cancer Research Fund) and Drs P. Jeffery and G. Laurent (both of the National Heart and Lung Institute) have kindly provided summaries of their presentations which were: 'An introduction to the cytokines', 'Cytokines and asthma', and 'Cytokines and pulmonary fibrosis' respectively. For completeness, the following paragraphs briefly highlight some of the major points from the presentations of the remaining invited speakers.
Measurement of cytokines in clinical samples STEPHEN POOLE, National Institute for Biological Standards and Control In this presentation, we learnt the relative advantages and disadvantages of bio- and immunoassays for cytokines. We were also reminded that a bioassay and an immunoassay for the same cytokine rarely yield identical results, since, of course, they are measuring different things. For example, the presence of an antagonist to a cytokine receptor in a biological sample, will reduce the bioactivity of that cytokine, but may or may not affect its immunoreactivity, Complex biological samples such as lung lavage and plasma contain many substances which can block antibody binding sites or conversely, to which antibodies may adhere non-specifically. Dr Poole therefore stressed the importance of adopting a meticulous and stringent approach to the development of new irnmunoassays. He emphasized that, to ensure specificity, the assay must give parallel standard curves in biological fluids and in a simple model system.
Cytokine networks in the lung STEVEN KUNKEL, Ann Arbor, Michigan, U.S.A. Our first overseas speaker, Professor Kunkel, expounded on the involvement of cytokine networks in the maintenance of chronic inflammation in several experimental models in the mouse lung. Intravenous injection of Sephadex beads carrying a purified protein derivative from Mycobacterium embolize in the lung provoking a THI lymphocyte-driven response, characterized by the production of IL-2 and I F N 7. In contrast, if the beads are linked to an antigen isolated from eggs of Schistosoma mansoni, the response is Tn2-1ymphocyte driven, characterized by IL-1 synthesis and results in the production of long-lasting pulmonary granulomata. Interestingly, in the latter model, levels of IL-1 receptor antagonist (IRAP) rise as those of IL-1 activity fall. Passive immunization of the animals to remove the IRAP results in an increased growth of the granulomata, indicating that the local synthesis and release of this antagonist is an important check to limit granuloma size. Professor Kunkel discussed the roles of a number of cytokines in experimental and clinical models of chronic pulmonary inflammation. Intravenous dosing with Sephadex beads impregnated with IL-4 or MCP-1 (monocyte chemotactic peptide) induced the development of granulomata, IL-4 acting indirectly by inducing the synthesis of MCP-1 and hence, attracting the mononuclear cells which are prerequisites of granuloma formation. Interestingly, MCP-1 is made by lung fibroblasts from patients with a granulomatous disease, sarcoidosis, and is detectable at high levels in their lung lavage, but is not found in samples from bronchitic or control subjects. This supports the concept that MCP-1 may play a similar role in sarcoidosis to that seen in the animal model. Finally, the speaker stressed that there is considerable redundancy in the cytokine system and thus, inhibition or deletion of a single cytokine is unlikely to block chronic inflammation.