Mast cells are found in close association with blood vessels, and histamine is known to be a potent vasodilator in humans. It is now clear that mast cells form neuroeffector junctions and that one of the types of nerve involved is the peptide-containing primary afferent neurone (C fibre). Nerve stimulation produces vasodilation which is blocked by antihistamines or by depletion of mast cell histamine with compound 48/80. Nerve stimulation also releases histamine and degranulates mast cells. Substance P and other neuropeptides release histamine from isolated rat and human skin mast cells. The actions of substance P and calcitonin gene-related peptide in human skin are compatible with a role for these two peptides in neurogenic inflammation. The inflammatory effects of substance P in human skin are inhibited by antihistamines. The possible role of the mast cell in neurogenic inflammation is discussed.
1 Acoustic rhinometry is a relatively new method for objectively assessing nasal airway patency. In this paper we compare acoustic rhinometry with active posterior rhinomanometry.2 Twenty normal healthy volunteers underwent nasal challenge with either histamine or bradykinin, 100 ,ug to 1000 ,ug, and responses were assessed by acoustic rhinometry. A further 20 subjects received identical nasal challenges and responses were assessed by active posterior rhinomanometry. 3 On a subsequent occasion, the subjects challenged previously with histamine, were given the selective H1-receptor antagonist, cetirizine, 10 mg orally, 3 h before repeat nasal challenge with histamine, 100-1000 ,ug. Again, responses were assessed by active posterior rhinomanometry and acoustic rhinometry. 4 The acoustic reflection measurements and the nasal airway resistance measurements showed comparable, significant dose-related changes in nasal patency to both histamine and bradykinin. Pretreatment with cetirizine blocked the histamine-induced change in nasal patency as measured by both methods. 5 We conclude that acoustic rhinometry has a number of advantages over posterior rhinomanometry. It is quick to perform, requires minimal subject co-operation and gives a reliable objective, measurement of dose-related changes in nasal airway patency before and after pharmacological treatment.
There is good evidence that some vascular effects of inflammation in the skin are neurogenic and involve axon reflexes in the terminal arborizations of C-fibres containing substance P, neurokinin A and calcitonin gene-related peptide (CGRP). Substance P produces dose-related wheal and flare reactions in human skin. Neurokinin A induces wheal but little or no flare and is less potent than substance P. CGRP induces both wheal and flare but is also less potent than substance P. In addition, CGRP induces a slow-onset, intense vasodilatation in human skin which persists for several hours and is associated with leucocyte infiltration: a response which is not seen with substance P. Substance P also releases histamine from mast cells in the skin and the presence or absence of a role for histamine and mast cells in neurogenic inflammation in skin is discussed.
Lipopolysaccharide (LPS) caused a concentration-dependent increase of released and cell-associated interleukin-1 (IL-1) in resident peritoneal macrophages from the mouse. LPS was about 30 times more potent at stimulating the level of cell-associated IL-1 than it was at stimulating the release of IL-1. Human recombinant tumour necrosis factor-alpha (TNF-alpha) and the calcium ionophores A23187 and ionomycin induced a concentration-dependent increase of cell-associated IL-1 but failed to cause release of IL-1 at concentrations producing maximal stimulation of cell-associated IL-1. The phorbol ester, 4 beta-phorbol dibutyrate, stimulated the release of IL-1 from mouse macrophages but failed to induce an increase in cell-associated IL-1. Substance P, neurokinin A, neurokinin B, calcitonin gene-related peptide and platelet-activating factor did not increase the released or cell-associated IL-1 in mouse macrophages. These agents also failed to alter released or cell-associated IL-1 stimulated by LPS, 1 microgram ml-1. It appears that a calcium signal is sufficient for the transcription and translation of IL-1 mRNA but does not result in the secretion of biologically active forms of IL-1. Our data also indicate that different intracellular signals may control the release and the cell accumulation of IL-1. We conclude that inflammatory mediators may independently increase either the release of, or the cell accumulation of IL-1.
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