INTERLEUKIN-1-BETA, BUT NOT TUMOR-NECROSIS-FACTOR, ENHANCES NEUROGENIC VASODILATATION IN THE RAT SKIN - INVOLVEMENT OF NITRIC-OXIDE

被引:7
作者
HERBERT, MK [1 ]
HERING, S [1 ]
HOLZER, P [1 ]
机构
[1] GRAZ UNIV,DEPT PHARMACOL,A-8010 GRAZ,AUSTRIA
关键词
INTERLEUKIN; 1-BETA; TUMOR NECROSIS FACTOR; CAPSAICIN; NEUROGENIC INFLAMMATION; NITRIC OXIDE;
D O I
10.1139/y95-153
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In phenobarbitone-anesthetized rats the effects of interleukin 1 beta (IL-1 beta) and tumor necrosis factors (TNFs) were examined on the capsaicin-induced increase of plantar cutaneous blood flow in the rat hind paw as measured by laser Doppler flowmetry. IL-1 beta (0.5-500 pg) or TNF alpha or TNF beta (50-5000 pg) was injected subcutaneously into the left paws, while the right paws received vehicle (10 mu L) only. IL-1 beta was without effect on blood flow by its own but dose dependently enhanced the hyperemia due to capsaicin (0.3 mu g). TNFs failed to enhance the capsaicin-induced vasodilatation, although 5000 pg TNF alpha produced a transient increase of local blood flow. Indomethacin (10 mg/kg, i.p.) did not alter the capsaicin-induced vasodilatation but prevented IL-1 beta (50 pg) from augmenting the hyperemic response to capsaicin. Likewise, blockade of nitric oxide formation by N-G-nitro-L-arginine methyl ester (L-NAME) failed to affect the capsaicin-evoked vasodilatation but abolished its amplification by IL-1 beta. Systemic pretreatment with a neurotoxic dose of capsaicin reduced the capsaicin-induced hyperemia and prevented the facilitatory effect of IL-1 beta. The hyperemia evoked by intraplantar calcitonin gene related peptide (0.038-3.8 ng) was not altered by IL-1 beta (50 pg). These data indicate that IL-1 beta but not TNF enhances the cutaneous hyperemic response to capsaicin. This proinflammatory action arises from sensitization of afferent nerve endings and depends on nitric oxide and cyclooxygenase products as essential intermediates.
引用
收藏
页码:1075 / 1079
页数:5
相关论文
共 21 条
[1]  
ANTONI G, 1986, J IMMUNOL, V137, P3201
[2]   THE CONTRIBUTION OF CALCITONIN GENE-RELATED PEPTIDE (CGRP) TO NEUROGENIC VASODILATOR RESPONSES [J].
BRAIN, SD ;
HUGHES, SR ;
CAMBRIDGE, H ;
ODRISCOLL, G .
AGENTS AND ACTIONS, 1993, 38 :C19-C21
[3]  
CUNHA Q, 1992, BRIT J PHARMACOL, V107, P660
[4]  
DAVIS A, 1993, BRIT J PHARMACOL, V108, pP19
[5]   EFFECT OF GLUCOCORTICOIDS, MONOKINES AND GROWTH-FACTORS ON THE SPONTANEOUSLY DEVELOPING RESPONSES OF THE RABBIT ISOLATED AORTA TO DES-ARG9-BRADYKININ [J].
DEBLOIS, D ;
BOUTHILLIER, J ;
MARCEAU, F .
BRITISH JOURNAL OF PHARMACOLOGY, 1988, 93 (04) :969-977
[6]   ROLE OF INTERLEUKIN-1 IN INFECTIOUS-DISEASES [J].
DINARELLO, CA .
IMMUNOLOGICAL REVIEWS, 1992, 127 :119-146
[7]  
DONNERER J, 1990, NEUROENDOCRINE IMMUN, P69
[8]  
EASTGATE JA, 1988, LANCET, V2, P706
[9]   INTERLEUKIN-1-BETA AS A POTENT HYPERALGESIC AGENT ANTAGONIZED BY A TRIPEPTIDE ANALOG [J].
FERREIRA, SH ;
LORENZETTI, BB ;
BRISTOW, AF ;
POOLE, S .
NATURE, 1988, 334 (6184) :698-701
[10]   INHIBITION BY NEUROPEPTIDES OF INTERLEUKIN-1-BETA-INDUCED, PROSTAGLANDIN-INDEPENDENT HYPERALGESIA [J].
FOLLENFANT, RL ;
NAKAMURACRAIG, M ;
HENDERSON, B ;
HIGGS, GA .
BRITISH JOURNAL OF PHARMACOLOGY, 1989, 98 (01) :41-43