RT Journal Article
SR Electronic
T1 Involvement of Cytokines in Lipopolysaccharide-Induced Facilitation of CGRP Release from Capsaicin-Sensitive Nerves in the Trachea: Studies with Interleukin-1β and Tumor Necrosis Factor-α
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4742
OP 4748
DO 10.1523/JNEUROSCI.16-15-04742.1996
VO 16
IS 15
A1 Hua, Xiao-Ying
A1 Chen, Ping
A1 Fox, Alyson
A1 Myers, Robert R.
YR 1996
UL http://www.jneurosci.org/content/16/15/4742.abstract
AB Lipopolysaccharide (LPS), an endotoxin, produces pain behavior, inflammation, and changes in immune function. Many of these effects are secondary to the production of cytokines. In the present study, we investigated the effect of LPS on the releasing function of afferent terminals as measured by calcitonin gene-related peptide (CGRP) release in ex vivo perfused rat trachea, and examined the possible role of the cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) as intermediaries in this effect. Systemic injection of LPS (0.75 mg/kg, i.p.) in adult rats induced an increase in body temperature followed by hypothermia, indicating ongoing infection. We observed that capsaicin-induced (0.1 μm) tracheal CGRP release was significantly enhanced in the LPS-treated animals after 5 hr. This enhancement of the peptide release by LPS was blocked by IL-1β tripeptide antagonist Lys-d-Pro-Thr (10 μm) and mimicked by IL-1β and TNF-α (10–100 pg/ml), suggesting that the potentiating effect of LPS on CGRP release is mediated by generation of IL-1β and TNF-α. IL-1β-induced augmentation of CGRP release was blocked by Lys-d-Pro-Thr. Additionally, the cyclooxygenase inhibitor ketorolac (10 μm) significantly attenuated the facilitatory effects of LPS and IL-1β, indicating involvement of prostanoids. These findings suggest that endotoxin treatment generated cytokines such as IL-1β and TNF-α that regulated the peripheral releasing function of primary sensory afferents by sensitizing the terminals and facilitating peptide release. This effect is prostanoid dependent.