Historical Survey of Definitions and Concepts of Inflammation.- References.- The Inflammatory Reaction.- 1 A Brief History of Inflammation.- A. From the Origins to the 19th Century.- B. Earlier 20th Century.- C. Chemical Mediators: Further Development.- References.- 2 The Sequence of Early Events.- A. Introduction.- B. The Phenomena of the Initial Response to Injury.- I. Changes in Vascular Calibre and Flow.- 1. The Normal Microcirculation.- 2. The Changes Seen After Injury.- II. Increased Vascular Permeability.- 1. Normal Structure of Small Blood Vessels.- 2. Exchanges Across the Wall of Normal Small Vessels.- 3. The Effects of Histamine-Type Permeability Factors-Vascular Labelling.- 4. Increased Permeability in Other Types of Inflammation.- III. Leucocytic Emigration.- 1. Pavementing of Leucocytes.- 2. Leucocytic Emigration.- 3. Chemotaxis.- 4. Mediators of Leucocytic Emigration.- C. Subsequent Course of the Inflammatory Reaction.- I. Resolution.- 1. Inflammatory Exudate.- 2. Polymorphs.- 3. Fibrin.- 4. Dead Tissue Cells.- II. Suppuration.- References.- 3 Mononuclear Phagocytes in Inflammation.- A. Nomenclature of Mononuclear Phagocytes.- B. Approaches to the Characterisation of Mononuclear Phagocytes.- I. Morphology.- II. Cytochemical Characterisation.- III. Functional Characterisation.- IV. Culture Characteristics.- C. The Characteristics of Mononuclear Phagocytes in Relation to Those of Other Cells.- D. Functions of Mononuclear Phagocytes.- E. Origin and Kinetics of Mononuclear Phagocytes During the Normal Steady State.- F. Origin and Kinetics of Mononuclear Phagocytes During an Inflammatory Response.- I. Acute Inflammation.- II. Chronic Inflammation.- G. The Effects of Anti-Inflammatory Drugs.- I. Glucocorticosteroids.- II. Azathioprine.- H. Humoral Control of Monocytopoiesis During Inflammation.- I. The Mononuclear Phagocyte System and Disease.- References.- 4 The Adhesion, Locomotion, and Chemotaxis of Leucocytes.- A. Introduction.- B. Leucocyte Adhesion.- I. General Considerations.- II. Studies of the Adhesion of Leucocytes.- C. Leucocyte Locomotion.- I. Morphological Observations.- II. Contact Inhibition of Movement.- III. Redistribution of Membrane in Moving Cells.- D. Chemotaxis.- I. Chemotaxis and Chemokinesis.- II. Methods for Measuring Leucocyte Chemotaxis.- III. Methods by Which Cells Detect Gradients.- IV. Chemoattractants.- 1. Products of Specific Immune Reactions.- 2. Non-Specific Endogenous Factors.- 3. Exogenous Chemoattractants.- V. Possible Models of Action of Chemoattractants at the Cell Membrane.- VI. Motor Mechanisms in Leucocyte Locomotion and Chemotaxis.- VII. Other Biochemical Mechanisms.- 1. Energy Sources for Locomotion.- 2. Cyclic Nucleotides.- 3. Protein and Nucleic Acid Synthesis.- 4. Effects of Other Agents.- VIII. Migration of Individual Leucocyte Types.- 1. Neutrophils and Mononuclear Phagocytes.- 2. Eosinophils.- 3. Lymphocytes.- IX. Does Chemotaxis Occur in vivo?.- References.- Addendum.- 5 Platelet Aggregation Mechanisms and Their Implications in Haemostasis and Inflammatory Disease.- A. Introduction.- B. Relationship of Morphology to Physiological Function in the Blood Platelet.- I. The Amorphous Coat.- II. The Trilaminar Plasma Membrane.- III. The Surface-Connecting (Open Channel or Cannicular) System.- IV. The Dense-Tubular System.- V. Microtubules.- VI. Microfilaments.- VII. Granules.- VIII. Organelles Concerned With Carbohydrate, Protein and Lipid Metabolism.- C. Mechanisms of Platelet Aggregation.- I. Adhesion and Spreading.- II. The Shape Change.- III. Aggregation.- IV. The Platelet Release Reaction.- V. An Outline of Methods for Studying Platelet Aggregation and Related Processes.- VI. Mechanisms of Platelet Aggregation.- 1. Semantics-First and Second Phase Aggregation.- 2. Mechanisms of Directly Induced Platelet Aggregation.- 3. The Labile Aggregation-Stimulating Substances (LASS) Derived From Arachidonic Aci.- 4. Mechanisms of Aggregation Induced Indirectly (i.e. Mediated Through Pro-Aggregatory Platelet Substances).- 5. Special Cases (e.g. Zymosan and Ristocetin.- D. The Role of Platelets in Haemostasis and Haemostatic Defects.- I. Events Occurring in Haemostasis.- II. Haemostatic Defects.- 1. Thrombocytopenia (Decreased Level of Circulating Platelets).- 2. Afibrinogenemia.- 3. Von Willebrand's Disease.- 4. Bernard Soulier (Giant Platelet) Syndrome.- 5. Thrombasthenia.- 6. Storage Pool Disease.- 7. Congenital Aspirin-Like Defects in Aggregation.- 8. Other Platelet Abnormalities.- E. The Role of Platelets in Inflammatory Processes.- I. The Platelet as a Source of Pro-Inflammatory Material.- 1. Mediators of Acute Inflammation Released From Platelets.- 2. Chemotactic Factors From Platelets.- 3. Cationic Proteins and Peptides Which Induce Increased Vascular Permeability.- 4. Pro-Inflammatory and Autolytic Enzymes From Platelets.- II. Evidence for Participation of Platelets in Various Inflammatory Diseases.- 1. Acute Inflammatory Responses Induced in the Rat by Non-Immunological Mechanisms.- 2. Inflammation Produced by Immunological Mechanisms.- F. Concluding Remarks.- I. Haemostasis.- II. Platelet Aggregation Mechanisms.- III. Inflammation.- References.- 6 Regeneration and Repair.- A. The Replacement of Lost Tissue.- I. Tissues Capable of Regeneration.- II. Tissues Incapable of Adequate Regeneration.- B. The Nature of the Stimulus Leading to Formation of Scar Tissue.- C. The Generation of Scar Tissue.- I. Generation of Scar Tissue in the Presence of Fibrin.- II. Generation of Scar Tissue in the Absence of Fibrin.- D. Stages in Scar Tissue Formation.- I. Formation of Capillaries.- II. The Formation of Connective Tissue.- 1. The Cells Involved.- 2. The Non-Fibrous Components of Connective Tissue.- 3. The Fibrous Components of Connective Tissue.- E. The Maturation of Scar Tissue: Contraction.- F. Abnormalities of Scar Tissue.- I. Keloids and Hypertrophic Scars.- II. Dupuytren's Contracture.- III. Scleroderma: Systemic Sclerosis.- IV. Drug-Induced Fibrosis.- G. Healing of Specialised Tissues.- Summary.- References.- 7 Immunological and Para-Immunological Aspects of Inflammation.- A. Introduction.- B. Mechanisms of Reactions in the Skin, Joints, and Body Cavities.- I. Complement-Dependent.- 1. Classical Pathway of Complement Activation.- 2. The Arthus Reaction.- 3. The Alternative Pathway of Complement Activation.- 4. Non-Specific Reactions to Endotoxin and the Local Shwartzman Phenomenon.- II. Cell-Mediated Immunity.- C. Complement-Dependent Inflammation-Classical Pathway.- I. Arthus Reaction.- 1. Experimental.- 2. Clinical.- II. Circulating Immune Complexes.- 1. Experimental.- 2. Clinical.- D. Complement-Dependent Inflammation-Alternative Pathway.- 1. Local Skin Inflammation-Local Shwartzman Reaction.- 2. The Effect of Intravenous Injection of Endotoxin-The Generalised Shwartzman Reaction.- E. Delayed Hypersensitivity.- 1. Jones-Mote vs. Tuberculin-Type Reactivity-Normal Homeostasis by Suppressor Cells.- 2. Humoral Antibody Reactions Resembling Delayed Hypersensitivity.- 3. Granuloma Formation.- F. Endogenous Antigen and Autoimmune Phenomena in Acute and Chronic Inflammation.- G. Allergic Arthritis.- 1. Experimental Models.- 2. Arthritis in Swine.- H. The Inflammatory Response in the Pleural Cavity.- 1. As an Experimental Model for Inflammation of Serosal Surface Including the Synovia.- 2. The Arthus Reaction.- 3. Cell-Mediated Immunity.- I. New Experimental Models for the Assay of Anti-Inflammatory Drugs.- References.- 8 The Release of Hydrolytic Enzymes From Phagocytic and Other Cells Participating in Acute and Chronic Inflammation.- A. Mechanism of Release of Hydrolytic Enzymes From Cells.- I. Lysis of Membranes.- II. Selective Release of Hydrolytic Enzymes Following Membrane Fusion.- B. The Selective Release of Acid Hydrolases by Polymorphonuclear Leucocytes.- I. Factors Influencing Enzyme Release.- II. Mechanism of Selective Release of Acid Hydrolases From Polymorphonuclear Leucocytes.- III. Selective Release of Lysosomal Enzymes From Polymorphonuclear Leucocytes by Factors Generated During Inflammatory Responses.- 1. Immune Complexes.- 2. Components of the Complement System.- IV. Lysis of Polymorphonuclear Leucocytes by Toxic Particles.- C. Blood Platelets.- D. Macrophages.- I. Selective Release of Acid Hydrolases by Macrophages.- 1. The Direct Interaction With Macrophages of Substances Which Cause Chronic Inflammation of a Non-Immunological Nature.- 2. The Release of Macrophage Lysosomal Enzymes by Products of Immune Reactions.- II. Secretion of Neutral Proteinases by Macrophages.- 1. Collagenase.- 2. Ekstase.- 3. Plasminogen Activator.- III. Secretion of Lysozyme by Macrophages.- E. Secretion of Lysosomal Enzymes by Cells of Soft Connective Tissue.- F. Effect of Released Enzymes on Macromolecular Natural Substrates.- I. Degradation of Connective Tissue Components.- II. Generation of Inflammatory Mediators by Hydrolytic Enzymes.- G. The Effects of Drugs on the Release of Hydrolytic Enzymes at Sites of Inflammation.- I. Steroid Anti-Inflammatory Drugs.- II. Nonsteroid Anti-Inflammatory Drugs.- References.- 9 Lysosomal Enzymes.- A. Lysosomes as Organelles.- B. Polymorphonuclear Leucocyte Lysosomes.- I. Granule Type.- II. Vacuolar Apparatus and Types of Lysosomes.- C. Lysosomes, Polymorphonuclear Leucocytes, and Inflammation.- D. Lysosomal Enzymes as Mediators of Inflammation and Tissue Injury.- I. Acid Proteinases.- II. Neutral Proteinases.- III. Other Lysosomal Enzymes.- IV. Collagenase.- E. Non-Enzymatic Mediators of Inflammation.- F. Regulation of Lysosomal Enzyme Release From Phagocytic Cells.- G. Summary.- References.- 10 Lymphokines.- A. Discovery and Definition.- B. Method of Production.- C. Biological Actions and Bioassay.- I. Lymphocyte Transformation.- II. Macrophage Activation.- III. Skin Response.- IV. Chemotaxis.- V. Other Lymphokine Actions.- D. Lymphokine Heterogeneity.- E. Modification of Lymphokine Production and Action by Drugs.- F. Relevance of Lymphokines to Inflammation.- Conclusion.- References.- Inflammatory Mediators Released From Cells.- 11 Histamine, 5-Hydroxytryptamine, SRS-A: Discussion of Type I Hypersensitivity (Anaphylaxis).- A. Immediate Hypersensitivity: General Considerations.- B. IgE and Other Antibodies Capable of Triggering Mast Cells and Basophils.- C. Mast Cells, Basophils, and Platelets.- D. Biochemistry of Release.- E. Assay of Mediators.- F. Histamine.- G. 5-Hydroxytryptamine.- H. SRS-A.- I. Summary: In vivo Significance of Mediators.- References.- 12 Prostaglandins and Related Compounds.- A. Introduction.- B. Reasons for Studying the Metabolism of Polyoxygenated Fatty Acid Derivatives.- C. A Note on Nomenclature.- I. Enzyme Nomenclature.- II. Fatty Acid Nomenclature.- III. Prostaglandin Nomenclature.- D. Nature and Origin of Fatty Acid Substrates for the Cyclo-Oxygenase.- E. Nature and Location of the Cyclo-Oxygenase.- F. Distribution of the Cyclo-Oxygenase.- G. Chemical Transformations Catalysed by the Cyclo-Oxygenase.- I. Generation of the Cyclic Endoperoxides.- II. Transformation of the Endoperoxide to HHT.- III. Transformation of the Endoperoxide to PGs.- IV. Transformation of the Endoperoxide to Thromboxane 'A' and 'B' (PHD).- V. Other Products Formed by the Cyclo-Oxygenase.- H. Enzymology of the Cyclo-Oxygenase.- I. Purification of the Enzyme.- II. Co-Factor Requirements.- III. Conditions for Optimal Activity.- IV. Turnover and Replacement of the Cyclo-Oxygenase.- V. Miscellaneous Remarks.- VI. Summary.- I. Turnover of Prostaglandins.- J. Lipoxygenase.- I. Distribution of the Enzyme.- II. Nature and Location of the Enzyme.- III. Chemical Transformations Catalysed.- IV. Formation of HPETE (Hydroperoxy Acid).- V. Formation of HETE (Hydroxy Acid).- VI. Enzymology of the Lipoxygenase.- K. Prostaglandin Inactivation.- I. Chemistry of Prostaglandin Catabolism.- II. Tissue Distribution of Catabolising Enzymes.- III. Other Metabolic Transformations.- L. Metabolism of Other Compounds.- M. Inhibition of Substrate Release From Phospholipids.- N. Inhibition of the Cyclo-Oxygenase.- O. Inhibition of Prostaglandin Inactivation.- P. Inhibition of Lipoxygenase.- Q. Summary.- References.- Inflammatory Mediators Generated by Activation of Plasma Systems.- 13 Complement.- A. Introduction.- B. Classical Activating Pathway.- C. Alternative Pathway.- I. Amplification Convertase.- II. Activation.- D. Effector Sequence.- E. Control of the Complement Reaction.- I. Cl?INH.- II. Anaphylatoxin Inactivator (AI).- F. Phylogeny.- G. Biological Activity of Complement.- I. Permeability Factors.- II. Chemotactic Factors.- III. Leucocyte Mobilizing Factor.- IV. Adherence Reactions.- H. Complement in Experimental Tissue Injury.- I. Complement in Human Disease.- I. Genetic Abnormalities.- II. Acquired Abnormalities.- K. Pharmacological Agents.- I. Activators.- II. Inhibitors.- References.- 14 Bradykinin-System.- A. Introduction.- B. Bradykinin System.- I. Kininogens.- 1. Kininogen Levels and Kininogen Depletion.- 2. Effect of Catecholamines on Kininogen Levels.- II. Kininogenases and the Release of Kinins.- 1. Plasma and Glandular Kallikreins.- 2. Plasmin.- 3. Other Proteolytic Enzymes.- 4. Generation of Kinins.- III. Kininases.- 1. Kininases in Biological Materials.- 2. Carboxypeptidase B and Chymotrypsin.- IV. Summary.- C. Involvement of Kinins in Inflammatory Reactions.- I. Effects of Kinins Related to the Signs and Symptoms of Inflammation.- 1. Vasodilation.- 2. Permeability-Increasing Action.- 3. Oedema.- 4. Production of Pain.- 5. Leucocyte Accumulation.- II. Release of Kinins by Trauma.- 1. Thermal Injury.- 2. Changes in Lymph Resulting From Burns.- 3. Chemical Injury.- 4. Electrical Stimulation and Interference of Nervous Structures.- 5. Micro-Organisms.- 6. Anaphylaxis.- D. Intervention of Cells in the Release and Destruction of Kinins.- E. Cell Proliferation and Tissue Repair.- F. Kinins and Disease.- I. Rheumatoid Arthritis.- II. Acute Gouty Arthritis.- III. Bronchial Asthma.- IV. Pancreatitis.- V. Miscellaneous.- G. Effect of Drugs on Kinin System and Consequences in Inflammatory Reactions.- I. Interference With the Actions of Kinins.- II. Interference With the Generation of Kinins.- III. Potentiating and Destroying Agents.- IV. Anti-Inflammatory Drugs and Experimental Inflammation.- H. Conclusions.- References.- 15 Endogenous Modulators of the Inflammatory Response.- A. New Look at an Old Phenomenon.- I. Terminology: By Way of Questioning What is a Modulator?.- II. Homeostatic Function and Self-Limiting Nature of Inflammation.- B. Counter-Irritation.- I. Inflammations Responsive and Non-Responsive to Counter-Irritation.- II. Components of Inflammation Susceptible and Non-Susceptible to Counter-Irritation.- III. Stimulants and Tissue Sites to Trigger Counter-Irritation.- IV. Modulating Mechanisms Triggered by Counter-Irritation.- C. Humoral Factors as Modulators.- I. Local Tissue Factors.- II. Plasma Factors.- III. Hepatic Factors.- IV. Endocrine Factors (Adrenal Steroids, Oestrogens, Insulin).- V. Mediators as Modulators: Role of the Cyclic Nucleotides.- D. Neurogenic Factors as Modulators.- I. Peripheral Nervous System: Neurotransmitters and Other Factors.- II. Central Nervous Influences.- E. Automodulation and Therapy.- I. Automodulation and Present Drugs.- II. Automodulation: A Possible Guide to New Drugs?.- References.- Contribution of the Inflammatory Mediators to the Signs and Symptoms of Inflammation.- 16 Inflammatory Mediators and Vascular Events.- A. Introduction.- B. Criteria for Implicating a Particular Mediator in the Production of Specific Effects.- I. Mediator Released in Adequate Amounts at Right Time.- II. Mediator Produces Effect When Administered in Reasonable Concentration.- III. Effect Blocked by Specific Blocking Agents.- IV. Prevention of Release Prevents Effects.- V. Prevention of Breakdown of Mediator Enhances Effect.- C. Difficulties With the Above.- I. Limitations of Methods of Detection and Identification.- II. Ubiquity of Mediators, Extraction Artefacts.- III. Possible Involvement of Potent Short-Lived Compounds.- IV. Interactions Between Mediators, Dual Mechanisms, Release One by Another.- V. Effect of Other Factors.- VI. Specificity of Different Inflammatory Models, Difficulties in Extrapolation.- VII. Species Variation, Strain, Site, etc.- VIII. Doubts on Specificity of Blockers.- D. Vascular Events Possibly Mediated by Endogenous Agents and Methods of Measuring Them.- I. Vasoconstriction, Vasodilatation, Changes in Blood Flow.- II. Pressure Changes in the Microcirculation, Filtration, Oedema, Stasis.- III. Permeability Changes.- IV. Leucocyte/Endothelium and Platelet/Endothelium Interactions.- E. Summary and Conclusions.- References.- 17 Pain and Inflammatory Mediators.- A. Introduction.- B. Measurement of Pain in Inflammation.- C. PainReceptors.- D. Chemical Stimulation of Pain Receptors.- E. Sensitization of Pain Receptors: Hyperalgesia.- F. Prostaglandin Release During Inflammation.- I. Prostaglandins and Pain.- II. Prostaglandins and Hyperalgesia.- G. Aspirin-Like Drugs and Their Mechanism of Analgesia.- References.- 18 Prostaglandins and Body Temperature.- A. An Introduction on Fever.- I. Exogenous Pyrogens.- II. Endogenous Pyrogens.- III. Pyrogen Injections Into the Liquor Space or Into Discrete Regions of the Brain.- IV. The Problem of Pyrogens Entering the CNS.- B. Temperature Responses to Prostaglandins in Different Species.- I. Temperature Responses in Cats.- II. Temperature Responses in Rabbits.- III. Temperature Responses in Monkeys.- IV. Temperature Responses in Humans.- V. Temperature Responses in Sheep.- VI. Temperature Responses in Rats.- VII. Temperature Responses in Mice.- VIII. Temperature Responses in Echidna (Tachyglossus aculeatus).- IX. Temperature Responses in Birds.- C. Temperature Effects of Prostaglandins at Different Ambient Temperatures.- D. Effect of Prostaglandins on Thermosensitivity of the Anterior Hypothalamus and on the Firing Rate of its Neurones.- E. Effects of Drugs on Prostaglandin Fever.- I. Antipyretics.- II. Prostaglandin Antagonist.- III. Drugs Which Deplete the Stores of the Monoamines or Block Their Actions.- IV. Atropine, Benztropine, Mecamylamine, and D-Tubocurarine.- V. Morphine and Chlorpromazine.- VI. Anaesthetics.- VII. Theophilline and Nicotinic Acid.- F. Prostaglandin Fever and Cyclic AMP.- G. Prostaglandin in CSF and Fever.- I. Endotoxin Fever.- II. Lipid A Fever.- III. Newcastle Disease Virus Fever.- IV. Endogenous Pyrogen Fever.- V. Variations in Increased Prostaglandin Activity During Endotoxin Fever and the Effect of Pentobarbitone Sodium Anaesthesia.- VI. An Unspecific Fever.- VII. Sodium Fever.- H. Febrile Episodes in Schizophrenia.- I. The Evidence for and Against the Prostaglandin Theory of Fever.- References.- Author Index.