Substance P and calcitonin gene-related peptide increase IL-1 beta, IL-6 and TNF alpha secretion from human peripheral blood mononuclear cells.
We found that substance P (SP) and calcitonin gene-related peptide (CGRP) (0.3-1 microM) increased, in a concentration-dependent manner, the basal secretion of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) from cultured lymphocyte-enriched mononuclear cells isolated from human peripheral blood. SP and CGRP (0.1 microM) synergistically increased basal TNF alpha secretion. Dynorphin A((1-17)) (0.1-1 microM) did not modify basal cytokine secretion. Lipopolysaccharide (10 ng/ml)-induced cytokine secretion and [(3)H]thymidine uptake were not altered by any neuropeptide (at 0.1 microM). Thus, SP and CGRP stimulate the production of pro-inflammatory cytokines from lymphocytes only at high concentrations, similar to those reached during tissue damage.
Cuesta
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MC
Section of Pharmacology, Instituto de Investigaciones Clínicas y Centro de Cirugía Experimental, Facultad de Medicina, University of Zulia, Apartado Postal 1151, Maracaibo 4001-A, Venezuela.
Quintero
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Pons
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Suarez-Roca
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H
D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004399:Dynorphins / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D004399:Dynorphins; D015740:Calcitonin Gene-Related Peptide; D013755:Tetradecanoylphorbol Acetate