Stimulation and release of interleukin-1 from peritoneal macrophages of the mouse

Abstract

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.

Neuropeptides

“…Similar results were obtained by Rameshwar et al, 67 who showed that SP mediated the release of IL-1 and IL-6 by bone marrow mononuclear cells. In contrast, Bahl and Foreman 68 demonstrated that SP did not cause either the release or the accumulation of IL-1 from murine peritoneal macrophages. Similarly, Lieb and coworkers 69 showed that SP and other neuropeptides were unable to induce the synthesis of IL-1 and IL-6 in human peripheral blood monocytes.…”

Do only circulating pyrogenic cytokines act as mediators in the febrile response? A hypothesis

“…In addition to the secreted forms, it is well known that cellassociated forms of proinflammatory cytokines are bioactive and exert potent effects [42,43]. Recent studies have shown that LPS [44], staphylococcal enterotoxin B [45] and live bacteria [46] induce high levels of cell-associated cytokines. Stimulation of endothelial cells by membrane-associated cytokines is well documented.…”

Neurokinin-1 Receptor Blockade and Murine Lung Tumorigenesis

“…It has been demonstrated that the neuropeptide SP is a potent effector of fibroblast migration and proliferation (3), which in conjunction with other factors (e.g., cytokines, reactive oxygen species) could worsen and accelerate the development of lung fibrosis. In particular, a neuropeptide regulation of proinflammatory and fibrogenic cytokine responses has been postulated and evidence has been reported demonstrating that SP can induce expression of tumor necrosis factor (TNF)-␣ (4,5) and interleukin (IL)-1 (6), two important mediators that can be found at an early stage after BLM treatment. SP released from sensory nerve terminals greatly contributes to neurogenic inflammation mainly by the activation of neurokinin-1 receptors (NK-1R) (7), which are widely expressed in lungs in several cell types including endothelial, epithelial, and smooth muscle cells, monocytes, macrophages, neutrophils, fibroblasts, and mast cells (8)(9)(10).…”