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Aging is associated with an overt inflammatory phenotype and physiological decline. Specialized proresolving lipid mediators (SPMs) are endogenous autacoids that actively promote resolution of inflammation. In this study, we investigated resolution of acute inflammation in aging and the roles of SPMs. Using a self-resolving peritonitis and resolution indices coupled with lipid mediator metabololipidomics, we found that aged mice had both delayed resolution and reduced SPMs. The SPM precursor docosahexaenoic acid accelerated resolution via increased SPMs and promoted human monocyte reprogramming. In aged mice, novel nano-proresolving medicines carrying aspirin-triggered resolvins D1 and D3 reduced inflammation by promoting efferocytosis. These findings provide evidence for age-dependent resolution pathways in acute inflammation and novel means to activate resolution.

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Mucosal surfaces function as selectively permeable barriers between the host and the outside world. Given their close proximity to microbial Ags, mucosal surfaces have evolved sophisticated mechanisms for maintaining homeostasis and preventing excessive acute inflammatory reactions. The role attributed to epithelial cells was historically limited to serving as a selective barrier; in recent years, numerous findings implicate an active role of the epithelium with proresolving mediators in the maintenance of immunological equilibrium. In this brief review, we highlight new evidence that the epithelium actively contributes to coordination and resolution of inflammation, principally through the generation of anti-inflammatory and proresolution lipid mediators. These autacoids, derived from ω-6 and ω-3 polyunsaturated fatty acids, are implicated in the initiation, progression, and resolution of acute inflammation and display specific, epithelial-directed actions focused on mucosal homeostasis. We also summarize present knowledge of mechanisms for resolution via regulation of epithelial-derived antimicrobial peptides in response to proresolving lipid mediators.

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IgA nephropathy, the most common form of primary glomerulonephritis, progresses to terminal renal failure in about 25% of patients 10 years after the apparent clinical onset. Since its description in 1968 an intense research effort in order to clarify the pathogenetic mechanisms has involved the study of animal models of the disease. In this review we analyze the experimental work reported since 1979, when the first animal model of IgA nephropathy was published by Rifai et al. We also discuss the interplay between experimental data and relevant clinical observations. Finally, we report the new insights about the role played by cytokines and growth factors.

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The aim of this review is that to examine some among the most important mediators involved in the onset of autacoid-mediated allergic and non-allergic symptomatology. Autacoids, such as histamine and arachidonic acid derivatives (leukotrienes and prostaglandins), mediators derived from cell membrane, such as PAF-acether and other cell-derived mediators, such as PF4, are described. Special importance is given to the respective pharmacological actions and to the mechanisms by which these actions are performed (receptors, antagonisms, synergism) from whose complexity systemic reactions might ensue. Furthermore, a part of this study is dedicated to the complex interactions among biochemical systems of the body such as Kinins, Coagulation, Fibrinolysis and Enzymatic Activity Mediators that can interfere with these interactions and support some pathologies. Besides, a chapter is devoted to Neurogenic Inflammation and therefore to Substance P and other neuropeptides.

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The pathochemical mechanisms of bronchospasm have been studied using various type of experimental allergies to microbial antigens. It was established that in guinea pigs with type I allergies isolated lung bronchospasm was mediated by histamine and SRS-A. Bronchial response to immune complexes type III were produced by the activation of complement with subsequent degranulation of mast cells and histamine release. Type IV hypersensitivity (lymphokine-mediated bronchospasm) was manifested without histamine, acetylcholine and mast cell involvement. The response to lymphokine was blocked by atropine. The spasmogenic y lymphokines are large molecular thermolabile substances.

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Rabbits were immunized with leukotriene C4 (LTC4) coupled to thiolated keyhole limpet hemocyanin (KLH) by using 6-N-maleimidohexanoic acid as a spacer molecule. Immune serum was obtained with 7.9 nmol of LTC4-specific immunoglobulin per milliliter and a mean association constant of 2.1 X 10(9) M-1. A radioimmunoassay was developed that detected 0.1 pmol of LTC4 per 1-ml sample. LTD4 and LTE4, three isomers of LTC4, the sulfones of LTC4, LTD4, and LTE4, and one isomer of LTD4 reacted to varying degrees in the assay. A number of other structurally related compounds, such as LTB4 and 5-HETE, did not react. Conditions were established to determine LTC4 levels in human plasma without loss of LTC4 during sample preparation and without the need for extraction procedures before the measurement of LTC4.

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Once considered only mediators of inflammation, autacoids, (histamine, prostaglandins and beta-mimetic catecholamines) have been found to be generated during specific early and late phases of immunity. They need sufficient concentrations to affect immunocytes and can modulate immunity usually by inhibiting it. Receptors for the autacoids on the immunocytes are nonrandomly distributed. A small portion of T suppressor cells always appear to have receptors on them, but precursor B cells and precursors of T cells that produce lymphokines or are responsible for cytolysis do not. Instead, as these cells mature they develop their autacoid receptors. With one exception, the function of the immunocytes is inhibited by the effects of autacoids. Again, in all but one instance, that inhibitory modulating effect is mediated by and directly proportional to the intracellular concentrations of cyclic adenosine monophosphate (AMP) generated by the autacoid. The clinical implications of these observations are beginning to be appreciated. One of them is that pharmacologic antagonists of the autacoids can have predictable but hitherto unanticipated effects on immune functions. It is inconceivable that these effects will not have clinical value.

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