Herbert M K, Hering S, Holzer P
Department of Anaesthesiology, University of Würzburg, Germany.
Can J Physiol Pharmacol. 1995 Jul;73(7):1075-9. doi: 10.1139/y95-153.
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 (50-500 pg) was injected subcutaneously into the left paws, while the right paws received vehicle (10 microL) only. IL-1 beta was without effect on blood flow by its own but dose dependently enhanced the hyperemia due to capsaicin (0.3 microgram). 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 NG-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.
在苯巴比妥麻醉的大鼠中，通过激光多普勒血流仪测量，研究了白细胞介素1β（IL-1β）和肿瘤坏死因子（TNFs）对辣椒素诱导的大鼠后爪足底皮肤血流增加的影响。将IL-1β（0.5 - 500 pg）或TNFα或TNFβ（50 - 500 pg）皮下注射到左爪，而右爪仅注射赋形剂（10 μL）。IL-1β自身对血流无影响，但剂量依赖性地增强了辣椒素（0.3 μg）引起的充血。TNFs未能增强辣椒素诱导的血管舒张，尽管5000 pg TNFα使局部血流短暂增加。吲哚美辛（10 mg/kg，腹腔注射）未改变辣椒素诱导的血管舒张，但阻止了IL-1β（50 pg）增强对辣椒素的充血反应。同样，NG-硝基-L-精氨酸甲酯（L-NAME）阻断一氧化氮形成未能影响辣椒素诱发的血管舒张，但消除了IL-1β对其的放大作用。用神经毒性剂量的辣椒素进行全身预处理可降低辣椒素诱导的充血，并阻止IL-1β的促进作用。足底注射降钙素基因相关肽（0.038 - 3.8 ng）引起的充血未被IL-1β（50 pg）改变。这些数据表明，IL-1β而非TNF增强了对辣椒素的皮肤充血反应。这种促炎作用源于传入神经末梢的敏化，并且依赖于一氧化氮和环氧化酶产物作为必需的中间体。
