Cao Ling, Hudson Chad A, Lawrence David A
Wadsworth Center, New York State Department of Health, Empire State Plaza, 12201-0509, Albany, NY, USA.
Brain Behav Immun. 2003 Apr;17(2):121-33. doi: 10.1016/s0889-1591(03)00026-6.
We previously reported that acute cold/restraint stress (ACRS) significantly inhibits host resistance to Listeria monocytogenes (LM) in BALB/c mice and that the sympathetic nervous system plays a major role in this inhibition. Here, we have further investigated the involvement of adrenergic receptor (ADR) subtypes. beta-ADR antagonist propranolol, but not alpha-ADR antagonist phentolamine significantly enhanced host resistance of ACRS mice. Pro-inflammatory cytokine (IL-6, IL-1beta, and TNFalpha) and IFNgamma levels positively correlated with the LM levels in all groups of mice. Furthermore, beta1-ADR antagonist atenolol but not beta2-ADR antagonist ICI118,551 significantly decreased LM burden in ACRS mice. In addition, SCID mice on the same genetic background (BALB/c), which have no adaptive immune potential, were used to assess the immune responses targeted by ACRS. ACRS-induced suppression of host resistance was not observed in SCID mice, and propranolol pretreatment provided no further improvement of host resistance, indicating that ACRS mainly affects adaptive immunity, which is less critical in mice with greater innate than adaptive immunity. In summary, the data suggest that ACRS inhibition of host resistance to LM is mediated through beta1-ADR stimulation, which appears to directly or indirectly modify activation of T cells or subsequent T cell functions involved in adaptive immunity, thus inhibiting overall host resistance. Interestingly, with heightened innate immunity and the absence of adaptive immunity, as observed in the SCID mice, ACRS does not affect host resistance, which emphasizes the importance of innate immunity in defense against bacterial infection.
我们之前报道过，急性冷/束缚应激（ACRS）显著抑制BALB/c小鼠对单核细胞增生李斯特菌（LM）的宿主抵抗力，且交感神经系统在这种抑制作用中起主要作用。在此，我们进一步研究了肾上腺素能受体（ADR）亚型的参与情况。β-ADR拮抗剂普萘洛尔可显著增强ACRS小鼠的宿主抵抗力，而α-ADR拮抗剂酚妥拉明则无此作用。在所有小鼠组中，促炎细胞因子（IL-6、IL-1β和TNFα）和IFNγ水平与LM水平呈正相关。此外，β1-ADR拮抗剂阿替洛尔可显著降低ACRS小鼠体内的LM负荷，而β2-ADR拮抗剂ICI118,551则无此作用。另外，利用具有相同遗传背景（BALB/c）且无适应性免疫潜能的重症联合免疫缺陷（SCID）小鼠来评估ACRS所靶向的免疫反应。在SCID小鼠中未观察到ACRS诱导的宿主抵抗力抑制，且普萘洛尔预处理也未进一步提高宿主抵抗力，这表明ACRS主要影响适应性免疫，而在先天免疫强于适应性免疫的小鼠中，适应性免疫的作用较小。总之，数据表明ACRS对宿主抵抗LM的抑制作用是通过β1-ADR刺激介导的，这似乎直接或间接改变了参与适应性免疫的T细胞激活或后续T细胞功能，从而抑制了整体宿主抵抗力。有趣的是，正如在SCID小鼠中观察到的那样，随着先天免疫增强且缺乏适应性免疫，ACRS并不影响宿主抵抗力，这强调了先天免疫在抵抗细菌感染中的重要性。
