Norepinephrine suppresses IFN-γ and TNF-α production by murine intestinal intraepithelial lymphocytes via the β₁ adrenoceptor.

We examined whether norepinephrine (NE) had direct effects on cytokine production by murine intestinal intraepithelial lymphocytes (IELs), compared with splenocytes. CD3⁺ IELs and CD3⁺ splenocytes expressed α(1B), α(1D), α(2C), β₁, β₂, and β₃ adrenoceptors (ARs). NE significantly suppressed IFN-γ and TNF-α production by IELs and splenocytes ex vivo. The suppressive effects of NE in IELs were reversed by β₁ AR antagonist CGP-20712A, whereas those in splenocytes were reversed by β₂ AR antagonist ICI118,551. In IELs, β₁ AR agonist xamoterol mimicked the suppressive effects of NE. These results indicated NE regulates intestinal mucosal immune responses mediated by IELs via β₁ AR.