Abstract
1. The effect of IL-1ra on response to intraplantar (i.pl.) injection of LPS, carrageenin, bradykinin, TNFalpha, IL-1beta, IL-8, PGE(2) and dopamine was investigated in a model of mechanical hyperalgesia in rats. 2. IL-1ra inhibited hyperalgesic response to LPS, carrageenin, bradykinin, TNFalpha, and IL-1beta, but not responses to IL-8, PGE(2) and dopamine. 3. A sheep anti-rat IL-1ra serum potentiated response to LPS, carrageenin, bradykinin, TNFalpha and IL-1beta but not IL-8. 4. Carrageenin and LPS stimulated and production of immunoreactive TNFalpha, IL-1beta and IL-1ra in the skin of injected paws. 5. The inhibition by IL-1ra of the hyperalgesic response to carrageenin was not affected by antibodies neutralizing IL-4 and IL-10. 6. In mice, IL-1ra inhibited the nociceptive response to i.p. injection of acetic acid. 7. These data suggest that IL-1ra, released at sites of inflammation, limits inflammatory hyperalgesia. This effect is independent of (IL-1ra-induced) IL-4 and IL-10 and appears to be the result of antagonism by IL-1ra of IL-1beta-stimulated eicosanoid production.
MeSH terms
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Acetic Acid / pharmacology
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Animals
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Antibodies / immunology
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Antibodies / pharmacology
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Bradykinin / pharmacology
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Carrageenan / pharmacology
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Cytokines / metabolism
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Cytokines / pharmacology*
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Dinoprostone / pharmacology
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Dopamine / pharmacology
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Dose-Response Relationship, Drug
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Hindlimb
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Hyperalgesia / metabolism
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Hyperalgesia / prevention & control*
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Immune Sera / pharmacology
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Inflammation / metabolism
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Inflammation / prevention & control*
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1 / metabolism
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Interleukin-1 / pharmacology
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Interleukin-10 / immunology
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Interleukin-4 / immunology
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Interleukin-8 / pharmacology
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Lipopolysaccharides / pharmacology
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Male
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Mice
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Pain Measurement
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Rats
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Rats, Wistar
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Sheep
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Sialoglycoproteins / immunology
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Sialoglycoproteins / metabolism
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Sialoglycoproteins / pharmacology*
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Skin / drug effects
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Skin / metabolism
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Antibodies
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Cytokines
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Il1rn protein, mouse
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Immune Sera
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1
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Interleukin-8
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Lipopolysaccharides
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Sialoglycoproteins
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Interleukin-4
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Carrageenan
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Dinoprostone
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Acetic Acid
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Bradykinin
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Dopamine