Yoshikawa T, Streilein J W
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
Reg Immunol. 1990;3(3):139-44.
Acute, low dose ultraviolet B (UVB) radiation impairs the induction of dinitrofluorobenzene (DNFB)-specific contact hypersensitivity (CH) in some, but not all, inbred strains of mice. Although C3H/HeN mice are UVB-susceptible by these criteria, the closely related strain, C3H/HeJ proved to be UVB-resistant. Since the only known important genetic difference between these strains is a polymorphism at the Lps locus which governs sensitivity to bacterial lipopolysaccharide (LPS), we examined the possibility that UVB radiation achieves its immune effects via an action directly or indirectly related to LPS. We found that intradermal injections of LPS failed to impair the induction of CH when DNFB was painted at the skin injection site. However, tumor necrosis factor-alpha (TNF alpha), a cytokine released from LPS-sensitive macrophages by exposure to LPS, was able to suppress CH induction when it was injected intradermally (50 ng) prior to epicutaneous application of hapten. In addition, systemic administration of larger doses of TNF alpha (200 ng) inhibited CH, whether the cytokine was injected intraperitoneally at the time of cutaneous sensitization with DNFB, or prior to ear challenge with the hapten. Importantly, when TNF alpha was injected into pinnae of DNFB-immune mice prior to elicitation of CH, local inflammatory responses were greatly exaggerated. Thus, TNF alpha shares with acute, low dose UVB radiation the following effects on CH: impairment of induction, and amplification of expression. These effects are only achieved following local treatment with these agents. We propose that TNF alpha is an important cytokine mediator of the effects of UVB on hapten-specific CH.
急性低剂量紫外线B（UVB）辐射会削弱某些（但并非所有）近交系小鼠对二硝基氟苯（DNFB）特异性接触性超敏反应（CH）的诱导。尽管按照这些标准C3H/HeN小鼠对UVB敏感，但与之密切相关的品系C3H/HeJ却被证明对UVB具有抗性。由于这两个品系之间唯一已知的重要遗传差异是Lps位点的多态性，该位点决定了对细菌脂多糖（LPS）的敏感性，我们研究了UVB辐射通过与LPS直接或间接相关的作用实现其免疫效应的可能性。我们发现，当在皮肤注射部位涂抹DNFB时，皮内注射LPS并不会削弱CH的诱导。然而，肿瘤坏死因子-α（TNFα），一种由对LPS敏感的巨噬细胞在接触LPS时释放的细胞因子，在皮内注射（50 ng）后，于表皮应用半抗原之前能够抑制CH的诱导。此外，全身给予更大剂量的TNFα（200 ng）会抑制CH，无论该细胞因子是在使用DNFB进行皮肤致敏时腹腔注射，还是在使用半抗原进行耳部激发之前注射。重要的是，当在引发CH之前将TNFα注射到DNFB免疫小鼠的耳廓中时，局部炎症反应会大大加剧。因此，TNFα与急性低剂量UVB辐射对CH具有以下共同作用：损害诱导以及放大表达。这些作用只有在使用这些试剂进行局部治疗后才能实现。我们提出TNFα是UVB对半抗原特异性CH作用的重要细胞因子介质。
