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Drug modulation of antigen‐induced paw oedema in guinea‐pigs: effects of lipopolysaccharide, tumour necrosis factor and leucocyte depletion
Author(s) -
Motta Joelson I. Braga,
Cunha Fernando Q.,
Vargaftig Bernardo Boris,
Ferreira Sergio H.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13038.x
Subject(s) - ovalbumin , histamine , pharmacology , azelastine , bradykinin , chemistry , lipopolysaccharide , leukotriene c4 , cetirizine , antagonist , leukotriene , medicine , endocrinology , immunology , antigen , receptor , asthma
1 In guinea‐pigs previously sensitized with ovalbumin, the intra‐plantar administration of the antigen induced dose‐dependent and sustained oedema. An intense infiltrate of neutrophils and eosinophils was observed at the peak of the oedema (4 h). 2 Oedema induced by ovalbumin at the doses of 50 or 200 μg/paw was not inhibited by antihistamines (meclizine and cetirizine), a PAF antagonist (BN 50730), a cyclo‐oxygenase inhibitor (indomethacin), a lipoxygenase inhibitor (MK‐886), a dual type lipo‐ and cyclo‐oxygenase inhibitor (NDGA), a bradykinin antagonist (Hoe 140) or the combination of cetirizine, MK‐886, indomethacin and BN 50730. These drugs did inhibit paw oedema induced by their specific agonists or by carrageenin. These results suggest that histamine, PAF, prostaglandins, leukotrienes or bradykinin are not important in the development of immune paw oedema in guinea‐pigs. 4 Dexamethasone (10 mg kg −1 ) inhibited oedema induced by ovalbumin (50 or 200 μg/paw, P < 0.05). This effect apparently does not result from inhibition of arachidonate metabolism, since indomethacin, MK‐886 and NDGA were without effect. 5 Oedema induced by ovalbumin (50 or 200 μg/paw) was also inhibited by azelastine. This effect was not due to the anti‐histaminic property of azelastine since two other potent‐antihistamines, meclizine and cetirizine, were ineffective. 6 Intravenous injection of lipopolysaccharide (LPS) dose‐dependently inhibited the oedema induced by ovalbumin (200 μg/paw). This effect could not be attributed to hypotension or leucopenia since the maximal dose applied (81 μg kg −1 ) did not induce significant changes in the blood pressure or in the white blood cell levels of the animals. It is suggested that the effect of LPS is mediated by the endogenous release of cytokines, including tumour necrosis factor (TNFα). Murine TNFα dose‐dependently (9–81 μg kg −1 ) inhibited the paw oedema induced by ovalbumin. 7 The anti‐oedematogenic effects of LPS and/or TNFα are possibly associated with their capacity to inhibit leucocyte emigration. Accordingly, guinea‐pigs rendered leucopenic with vinblastine exhibited less intense oedema after ovalbumin. Vinblastine did not affect oedema induced by PAF or bradykinin, indicating that vascular responsiveness was not involved.