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

In phenobarbitone-anesthetized rats the effects of interleukin 1 beta (IL-1 beta) and tumor necrosis factors (TNFs) were examined on the cap saicin-induced increase of plantar cutaneous blood flow in the rat hin d paw as measured by laser Doppler flowmetry. IL-1 beta (0.5-500 pg) o r 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. I L-1 beta was without effect on blood flow by its own but dose dependen tly enhanced the hyperemia due to capsaicin (0.3 mu g). TNFs failed to enhance the capsaicin-induced vasodilatation, although 5000 pg TNF al pha produced a transient increase of local blood flow. Indomethacin (1 0 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 indica te that IL-1 beta but not TNF enhances the cutaneous hyperemic respons e to capsaicin. This proinflammatory action arises from sensitization of afferent nerve endings and depends on nitric oxide and cyclooxygena se products as essential intermediates.