TUMOR-NECROSIS-FACTOR-ALPHA PREVENTS INTERLEUKIN-1-BETA FROM AUGMENTING CAPSAICIN-INDUCED VASODILATATION IN THE RAT SKIN

The effect of tumor necrosis factor-alpha (TNF alpha) and tumor necros is factor-beta (TNF beta) on the capsaicin-induced increase in cutaneo us blood flow was investigated in anaesthetized rats. Skin blood flow was measured by laser-Doppler flowmetry. Intraplantar subcutaneous inj ections of 5-500 pg TNF alpha and 50-5000 pg TNF beta had no effect on local blood flow, whereas 5000 pg TNF alpha induced a transient hyper aemia. However, neither the pretreatment with TNF alpha (5-5000 pg) no r that with TNF beta (50-5000 pg) enhanced the vasodilatator response to intraplantar capsaicin (0.03 pg; 0.1 mu g), whereas 50 pg interleuk in-1 beta augmented the capsaicin-induced hyperaemia (P < 0.05). This enhancement of the cutaneous hyperaemic response to capsaicin was abse nt when interleukin-1 beta (50 pg) was co-injected with TNF alpha (500 pg or 5000 pg). The vasodilatation caused by calcitonin gene-related peptide or bradykinin was not altered by 500 pg or 5000 pg TNF alpha. These data indicate that TNFs, in contrast to interleukin-1 beta, do n ot amplify the hyperaemic response to afferent nerve stimulation with capsaicin but reverse the augmentation mediated by interleukin-1 beta.